StemCell Therapy

- COSELA is the only FDA-approved therapy that helps proactively deliver multilineage myeloprotection to patients with extensive-stage small cell lung cancer being treated with chemotherapy -

- Myeloprotective efficacy of COSELA resulted in reductions in the incidence and duration of severe neutropenia, and impacted anemia and the need for rescue interventions such as growth factors and red blood cell transfusions -

- G1 will host conference call Tuesday, February 16, 2021 at 8:00 a.m. ET -

RESEARCH TRIANGLE PARK, N.C., Feb. 12, 2021 (GLOBE NEWSWIRE) -- G1 Therapeutics Inc. (Nasdaq: GTHX), a commercial-stage oncology company, today announced that the U.S. Food and Drug Administration (FDA) has approved COSELA(trilaciclib) for injection to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC). It is the first and only therapy designed to help protect bone marrow (myeloprotection) when administered prior to treatment with chemotherapy. COSELA is expected to be commercially available through G1s specialty distributor partner network in early March.

The approval of trilaciclib (COSELA) is an important advance in the treatment of patients with extensive-stage small cell lung cancer receiving chemotherapy, said Dr. Jeffrey Crawford, Geller Professor for Research in Cancer in the Department of Medicine and Duke Cancer Institute. The most serious and life-threatening side effect of chemotherapy is myelosuppression, or damage to the bone marrow, resulting in reduced white blood cells, red blood cells and platelets. Chemotherapy-induced myelosuppression may lead to increased risks of infection, severe anemia, and/or bleeding. These complications impact patients quality of life and may also result in chemotherapy dose reductions and delays.To date, approaches have included the use of growth factor agents to accelerate blood cell recovery after the bone marrow injury has occurred, along with antibiotics and transfusions as needed. By contrast, trilaciclib provides the first proactive approach to myelosuppression through a unique mechanism of action that helps protect the bone marrow from damage by chemotherapy.In clinical trials, the addition of trilaciclib to extensive-stage small cell lung cancer chemotherapy treatment regimens reduced myelosuppression and improved clinical outcomes.The good news is that these benefits of trilaciclib will now be available for our patients in clinical practice.

Chemotherapy is an effective and important weapon against cancer. However, chemotherapy does not differentiate between healthy cells and cancer cells. It kills both, including important hematopoietic stem and progenitor cells (HSPCs) in the bone marrow that produce white blood cells (immune cells that help fight infection), red blood cells (cells that carry oxygen from the lungs to the tissues), and platelets (cells that prevent bleeding from cancer, surgeries, chronic diseases, and injuries). This chemotherapy-induced bone marrow damage, known as myelosuppression, can lead to increased risk of infection, anemia, thrombocytopenia, and other complications. Myeloprotection is a novel approach of protecting HSPCs in the bone marrow from chemotherapy-induced damage. This approach can help reduce some chemotherapy-related toxicity, making chemotherapy safer and more tolerable, while also reducing the need for reactive rescue interventions.

Chemotherapy is the most effective and widely used approach to treating people diagnosed with extensive-stage small cell lung cancer; however, standard of care chemotherapy regimens are highly myelosuppressive and can lead to costly hospitalizations and rescue interventions, said Jack Bailey, Chief Executive Officer at G1 Therapeutics. COSELA will help change the chemotherapy experience for people who are battling ES-SCLC. G1 is proud to deliver COSELA to patients and their families as the first and only therapy to help protect against chemotherapy-induced myelosuppression.

COSELA is administered intravenously as a 30-minute infusion within four hours prior to the start of chemotherapy and is the first FDA-approved therapy that helps provide proactive, multilineage protection from chemotherapy-induced myelosuppression. The approval of COSELA is based on data from three randomized, placebo-controlled trials that showed patients receiving COSELA prior to the start of chemotherapy had clinically meaningful and statistically significant reduction in the duration and severity of neutropenia. Data also showed a positive impact on red blood cell transfusions and other myeloprotective measures. The trials evaluated COSELA in combination with carboplatin/etoposide (+/- the immunotherapy atezolizumab) and topotecan chemotherapy regimens. Approximately 90% of all patients with ES-SCLC will receive at least one of these regimens during the course of their treatment.

The majority of adverse reactions reported with COSELA were mild to moderate in severity.The most common adverse reactions (10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia. Serious adverse reactions occurred in 30% of patients receiving COSELA. Serious adverse reactions reported in >3% of patients who received COSELA included respiratory failure, hemorrhage, and thrombosis. Grade 3/4 hematological adverse reactions occurring in patients treated with COSELA and placebo included neutropenia (32% and 69%), febrile neutropenia (3% and 9%), anemia (16% and 34%), thrombocytopenia (18% and 33%), and leukopenia (4% and 17%), respectively.

Quite often, people diagnosed with extensive-stage small cell lung cancerrely on chemotherapy to not only extend their lives, but also to acutely alleviate their symptoms, said Bonnie J. Addario, lung cancer survivor, co-founder and board chair of the Go2 Foundation for Lung Cancer. Unfortunately, the vast majority will experience chemotherapy-induced side effects, resulting in dose delays and reductions, and increased utilization of healthcare services. G1 shares our organizations goal to improve the quality of life of those diagnosed with lung cancer and to transform survivorship among people living with this insidious disease. We are thrilled to see new advancements that can help improve the lives of those living with small cell lung cancer.

Approximately 30,000 small cell lung cancer patients are treated in the United States annually. G1 is committed to helping patients with extensive-stage small cell lung cancer in the U.S. gain access to treatment with COSELA. For more information on access and affordability programs, patients and providers should call the G1toOne support center at 833-G1toONE (833-418-6663) from 8:00 a.m. to 8:00 p.m. Eastern time.

G1 received Breakthrough Therapy Designation from the FDA in 2019 based on positive data in small cell lung cancer patients from three randomized Phase 2 clinical trials. As is common with breakthrough-designated products that receive priority review, G1 will conduct certain post-marketing activities, including in vitro drug-drug interaction and metabolism studies, and a clinical trial to assess impact of trilaciclib on disease progression or survival in patients with ES-SCLC with chemotherapy-induced myelosuppression treated with a platinum/etoposide-containing or topotecan-containing regimen with at least a two year follow up. G1 intends to initiate the post-approval clinical trial in 2022.

Webcast and Conference Call The management team will host a webcast and conference call at 8:00 a.m. ET on Tuesday, February 16, 2021 to discuss the FDA approval of COSELA (trilaciclib). The live call may be accessed by dialing 866-763-6020 (domestic) or (210) 874-7713 (international) and entering the conference code: 6195528. A live and archived webcast will be available on theEvents & Presentationspage of the companys website: http://www.g1therapeutics.com. The webcast will be archived on the same page for 90 days following the event.

COSELA (trilaciclib) Co-Promotion Agreement with Boehringer Ingelheim

InJune 2020, G1 announced a three-year co-promotion agreement withBoehringer Ingelheimfor COSELA in small cell lung cancer in theU.S.andPuerto Rico. G1 will lead marketing, market access and medical engagement initiatives for COSELA. The Boehringer Ingelheim oncology commercial team, well-established in lung cancer, will lead sales force engagement initiatives.G1 will book revenue and retain development and commercialization rights to COSELA and payBoehringer Ingelheima promotional fee based on net sales. The three-year agreement does not extend to additional indications that G1 is evaluating for trilaciclib. Press release details of the G1/Boehringer Ingelheimagreement can be foundhere.

About Small CellLung Cancer

In the United States, approximately 30,000 small cell lung cancer patients are treated annually. SCLC, one of the two main types of lung cancer, accounts for about 10% to 15% of all lung cancers. SCLC is an aggressive disease and tends to grow and spread faster than NSCLC. It is usually asymptomatic; once symptoms do appear, it often indicates that the cancer has spread to other parts of the body. About 70% of people with SCLC will have cancer that has metastasized at the time they are diagnosed. The severity of symptoms usually increases with increased cancer growth and spread. From the time of diagnosis, the general 5-year survival rate for people with SCLC is 6%. The five-year survival rates for limited-stage (the cancer is confined to one side of the chest) SCLC is 12% to 15%, and for extensive stage (cancer has spread to the other lung and beyond), survival rates are less than 2%. Chemotherapy is the most common treatment for ES-SCLC.

COSELA(trilaciclib) for InjectionINDICATIONCOSELA is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC).

IMPORTANT SAFETY INFORMATION

CONTRAINDICATION

WARNINGS AND PRECAUTIONS

Injection-Site Reactions, Including Phlebitis and Thrombophlebitis

Acute Drug Hypersensitivity Reactions

Interstitial Lung Disease/Pneumonitis

Embryo-Fetal Toxicity

ADVERSE REACTIONS

DRUG INTERACTIONS

To report suspected adverse reactions, contact G1 Therapeutics at 1-800-790-G1TX or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.

Please see full Prescribing Information here

For more information about COSELA, please call 1-800-790-G1TX (1-800-790-4189)

About G1 TherapeuticsG1 Therapeutics, Inc. is a commercial-stage biopharmaceutical company focused on the discovery, development and delivery of next generation therapies that improve the lives of those affected by cancer, including the Companys first commercially available product COSELA (trilaciclib), a first-in-class therapy approved by the U.S. Food and Drug Administration to help protect against chemotherapy-induced myelosuppression in patients with extensive-stage small cell lung cancer being treated with chemotherapy. Trilaciclib is also being evaluated in other solid tumors, including colorectal, breast and bladder cancers. G1 Therapeutics is based in Research Triangle Park, N.C. For additional information, please visit http://www.g1therapeutics.com and follow us on Twitter @G1Therapeutics.

Tecentriq (atezolizumab) is a registered trademark of Genentech.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate," "estimate," "intend" and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements in this press release include, but are not limited to, those relating to the therapeutic potential of COSELA (trilaciclib), and COSELAs (trilaciclib) possibility to improve patient outcomes, are based on the companys expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Factors that may cause the companys actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in the companys filings with theU.S. Securities and Exchange Commission, including the "Risk Factors" sections contained therein and include, but are not limited to, the companys ability to complete clinical trials for, obtain approvals for and commercialize any of its product candidates; the companys initial success in ongoing clinical trials may not be indicative of results obtained when these trials are completed or in later stage trials; the inherent uncertainties associated with developing new products or technologies and operating as a development-stage company; and market conditions. Except as required by law, the company assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

Contacts:Will RobertsG1 Therapeutics, Inc.Vice President, Investor Relations and Corporate Communications(919) 907-1944wroberts@g1therapeutics.com

Christine RogersG1 Therapeutics, Inc.Associate Director, Corporate Communications(984) 365-2819crogers@g1therapeutics.com

A PDF accompanying this announcement is available athttp://ml.globenewswire.com/Resource/Download/fb9c3593-c36f-4769-9c66-c1ca2e1f78f7

A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/25e03769-0cd1-482e-9a70-8b3c81bc46c3

COSELA (trilaciclib) image

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FDA Approves G1 Therapeutics' COSELA (trilaciclib): The First and Only Myeloprotection Therapy to Decrease the Incidence of Chemotherapy-Induced...

Drinking certain energy drinks may cause significant damage to the heart, according to new findings published in Food and Chemical Toxicology.

Because the consumption of these beverages is not regulated and they are widely accessible over the counter to all age groups, the potential for adverse health effects of these products is a subject of concern and needed research, lead researcher Ivan Rusyn, MD, PhD, a professor at Texas A&M University in College Station, said in a prepared statement.

Rusyn et al. assessed a total of 17 popular energy drinks, studying their chemical profiles and looking for any associations with potential cardiac complications. Energy drinks sold by Adrenaline, Shoc, Bang Star, C4, CELSIUS, HEAT, EBOOST, Game Fuel, GURU, Kill Cliff, Kickstart, Monster Energy, Red Bull, Reign, Rockstar, RUNA, UPTIME, Venom Energy and Xyience Energy were all part of the teams analysis.

Overall, the authors found that stem cell-derived cardiomyocyteshuman heart cells grown in a laboratoryshowed signs of an increased beat rate after being exposed to some energy drinks. Also, theophylline, adenine and azelate were all ingredients the team associated with potentially contributing to QT prolongation in cardiomyocytes.

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Energy drinks may damage the heart, researchers warnshould the FDA get involved? - Cardiovascular Business

Adeline Davidson and dad Jordan.Picture: Callum Mackay

THE Easter Ross mum of a little girl with an extremely rare form of blood cancer has urged life-saving donors to step up to help others.

Steph Davidson made the appeal as blood cancer charity DKMS asked people to show the love this Valentine's Day by signing up for a worldwide register of potential blood stem cell donors.

Her daughter Adeline (3) is awaiting a blood stem cell donation from a stranger and has endured many "false starts" and complications as a result of the coronavirus crisis.

Ms Davidson, who lives in Alness, is backing the DKMS campaign at a time when UK-wide registrations have slumped by 28 per cent.

Big-hearted Highlanders have bucked that trend with an increase in registrations during the pandemic.

With no match within her family, a blood stem cell donation from a complete stranger is Adelines best chance of survival.

The brave little girl, who has missed out on her first year at nursery and valiantly gone through painful and invasive treatment over the last year, has finally got a date for her lifesaving transplant.

With one donor pulling out at the last minute, and her transplant date pushed back several times due to the pandemic, her family have their heart set on finally having their healthy and happy little girl back home and able to play with her friends and family.

Her mum said: Shes such a sweet and friendly little girl, so confident and the best big sister to her little brother and sister. Its just felt like the world has been against us this past year with so many treatments, needles and false starts.

"We are so incredibly grateful to this stranger, who could be anywhere in the world. I want to give them the biggest hug in the world. I cant begin to imagine how awful it is for other families who have a loved one in need of a lifesaving transplant where no match has been found.

"As a parent it makes you feel so powerless being unable to protect your child. Anyone who is healthy and able to register, please, please do. Its such a small commitment for you and could give someone a second chance at life Adelines not even had a chance to start hers and we were so close to it being taken away from her.

The Valentines Day campaign by DKMS is asking people to celebrate with their loved one by taking five minutes to sign up to the stem cell donor register to potentially save the love of someone elses life.

Every 20 minutes, someone in the UK is diagnosed with blood cancer. Around 2000 people each year are dealt the shocking news that they need a blood stem cell transplant.

For these people the perfect match doesnt necessarily have a compatible Zodiac sign or share the same taste in films they need to have a genetically similar make up to give them the best shot at a second chance of life.

With two in three of those people not finding a perfect match within their family, they must turn to the worldwide donor registry and rely on a stranger to save their lives. By signing up to the register you could one day be a match for someone who needs you to help save their life.

The pandemic has had a destructive impact on the lives of people with blood cancer. Not only has it led to a huge drop in the number of people registering as donors, it has meant fewer people are visiting the GP with cancer symptoms, and resulted in hospital appointments and treatments being postponed or cancelled. Due to this, DKMS expects to see a surge in blood cancer diagnoses and increased demand for blood stem cell donors when we are back to normal, making it all the more important that people register now.

Jonathan Pearce, chief executive of DKMS UK, said: At DKMS, we are dedicated to the fight against blood cancer and are proud to have registered over 780,000 blood stem cell donors. Hearing the stories of people like Adeline shows why people registering as blood stem cell donors is so important.

"With the shocking drop in registrations over the last 10 months we are calling on Scots to save the love of someone elses life this Valentines Day. We want every worried family to get the reassuring call that a match for their loved on has been found. If youre inspired by Adelines story, please register as a stem cell donor to give the ultimate gift this Valentines Day by saving a life.

How to sign up

Signing up to save the life of someone like Adeline is easy to do. Register as a potential lifesaver online at dkms.org.uk to receive your home swab kit. It takes a few moments to swab. When you return your swab kit you go on standby to help save someones life.

Taking the first steps to register as a potential blood stem cell donor can be done within a few minutes from the comfort of your own home. If you are aged between 17-55 and in general good health you can sign up for a home swab kit online. Your swabs can then be returned with the enclosed pre-paid envelope to DKMS in order to ensure that your details are added to the UKs aligned stem cell registry.

Related: Alness parents make heartfelt plea after coronavirus-related donor blow

Waiting game as stem cell donor found in United States

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Easter Ross mum of blood cancer tot urges would-be stem cell donors to show the love this Valentine's Day; Alness lass Adeline Davidson's plight...

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Global Induced Pluripotent Market Positive Outlook, Revenue Generation & Leading Manufacturers, Forecast 2026||CELGENE CORPORATION; Astellas...

Leukemia is a type of cancer that affects the blood. The two most common types in children are acute lymphoblastic leukemia and acute myelogenous leukemia.

In a person with leukemia, blood cells are released into the bloodstream before they are fully formed, so there are fewer healthy blood cells in the body.

Below, we describe the types of childhood leukemia, the symptoms, and the treatments. We then look at when to contact a doctor, what questions to ask, and where to find support.

Childhood leukemia is the most common form of cancer in children. It affects up to 3,800 children under the age of 15 in the United States each year.

Leukemia occurs when bone marrow releases new blood cells into the bloodstream before they are fully mature.

These immature blood cells do not function as they should, and eventually, the number of immature cells overtakes the number of healthy ones.

Leukemia can affect red and white blood cells and platelets.

The bone marrow produces stem cells. A blood stem cell can become a myeloid stem cell or a lymphoid stem cell.

Lymphoid stem cells become white blood cells. Myeloid stem cells can become:

Leukemia is typically acute or chronic, and chronic types are rare in children. They can include chronic myeloid leukemia or chronic lymphocytic leukemia.

Most childhood leukemias are acute, meaning that they progress quickly and need treatment as soon as possible.

Acute lymphoblastic leukemia (ALL) is the most common type in children, accounting for 75% of childhood leukemia cases.

It affects cells called lymphocytes, a type of white blood cell.

In a person with ALL, the bone marrow releases a large number of underdeveloped white blood cells called blast cells. As the number of these increases, the number of red blood cells and platelets decreases.

There are two subtypes of ALL: B-cell and T-cell.

In most childhood cases of ALL, the cancer develops in the early forms of B-cells. The other type, T-cell ALL, typically affects older children.

Research from 2020 reports that the majority of people diagnosed with ALL are under 18 and typically between 2 and 10 years old.

The American Cancer Society report that children under 5 years old have the highest risk of developing ALL and that this risk slowly declines until a person reaches their mid-20s.

The outlook for ALL depends on the subtype, the persons age, and factors specific to each person.

Myeloid leukemias account for approximately 20% of childhood leukemia cases, and most myeloid leukemias are acute.

Acute myelogenous leukemia (AML) affects white blood cells other than the lymphocytes. It may also affect red blood cells and platelets.

AML can begin in:

Juvenile myelomonocytic leukemia (JMML) accounts for approximately 12% of leukemia cases in children.

This rare type is neither acute nor chronic. JMML begins in the myeloid cells, and it typically affects children younger than 2 years.

Symptoms can include:

The symptoms of leukemia may be nonspecific similar to those of other common childhood illnesses.

A doctor will ask how long the child has been experiencing the symptoms, which can include:

Children may experience specific symptoms depending on the type of blood cell that the leukemia is affecting.

A low number of red blood cells can cause:

A low number of healthy white blood cells can cause infections or a fever with no other sign of an infection.

A low platelet count can cause:

Various factors can increase a childs risk of leukemia, and most are not preventable.

The following genetic conditions can increase the risk of leukemia:

Also, having a sibling with leukemia may increase the risk of developing it.

These can include exposure to:

If a child has symptoms that might indicate leukemia, a doctor may perform or request:

A bone marrow aspiration involves using a syringe to take a liquid sample of bone marrow cells. The doctor may give the child a drug that allows them to sleep through this test.

During the diagnostic process, a person might ask:

The doctor may recommend a variety of treatments for childhood leukemia, and the best option depends on a range of factors specific to each person.

The treatment usually consists of two phases. The first aims to kill the leukemia cells in the childs bone marrow, and the second aims to prevent the cancer from coming back.

The child may need:

Before or during treatment, a person might ask the doctor:

Questions to ask after the treatment might include:

Children who have undergone leukemia treatments require follow-up care, as the treatments often cause late effects.

These can develop in anyone who has received treatment for cancer, and they may not arise for months or years after the treatment has ended.

Treatments that can cause late effects include:

These complications may affect:

The late effects that may come can also depend on the type of treatment and the form of leukemia.

Because many leukemia symptoms can also indicate other issues, it can be hard to know when to contact a doctor.

Overall, it is best to seek medical advice if a child shows symptoms or behaviors that are not normal for them.

If a child has received a leukemia diagnosis, the effects can extend to parents, other family members, caregivers, and friends.

A person can find support and additional resources from:

The following organizations based in the United Kingdom also provide support and guidance:

Childhood leukemia can affect mental health, as well as physical health.

Learn more about mental health resources here.

According to the American Cancer Society, most children with leukemia have no known risk factors. There is no way to prevent leukemia from developing.

Because there are very few lifestyle-related or environmental causes of childhood leukemia, it is very unlikely that a caregiver can do anything to help prevent the disease.

A childs outlook depends on the type of leukemia. It is important to keep in mind that current estimates do not take into account recent advances in technology and medicine.

For example, the most recent 5-year survival rate estimates reflect the experiences of children who received their diagnoses and treatments more than 5 years ago.

The American Cancer Society report that the 5-year survival rate for children with ALL is 90%. The same rate for children with AML is 6570%.

Childhood leukemia is typically acute, which means that it develops quickly. As a result, a person should contact a doctor if they notice any of the symptoms.

The most common type of childhood leukemia is ALL, representing 3 out of 4 leukemia cases in children.

Treatment may include a combination of chemotherapy, targeted drugs, immunotherapy, stem cell transplants, surgery, and radiation.

The prognosis depends on the type of leukemia and the childs age.

This diagnosis can affect mental as well as physical health, and the effects can extend to caregivers, family members, and friends. Many different resources are available for support.

More:
Leukemia in children: Symptoms, causes, treatment, outlook, and more - Medical News Today

Every year, about 10,000 people in the U.S. need a stem cell transplant but cant find a donor.

The intense medical procedure, which can help those with leukemia, lymphoma, sickle cell anemia and other blood diseases, can save lives but securing a donor can be like finding a needle in a haystack.

Be The Match is a nonprofit, national registry where people can sign up to donate their stem cells. More than 35 million people around the world have volunteered yet only a small percentage of those donors are Americans, and even the registry admits most Americans dont know it exists.

The mother of a 12-year-old boy with leukemia has set out to change that.

Mandy Goldman is a hairdresser who lives with her husband and four children outside Boston. She remembers the devastating day five years ago when doctors told her the chemotherapy they gave her son Mateo Goldman, 9 years old at the time, didnt work.

They told us that our only option of curing Mateo was a bone marrow transplant, she says, a risky procedure that often involves a host of complications. But they had no other choice, she says.

The family got to work on the monumental task finding Mateo Goldman a close enough match.

Linda Matchan first reported the Goldman familys experience for The Boston Globe. In her research, she found very, very few people had any awareness of the need for bone marrow and stem cells donors. The awareness campaign around the subject is severely lacking compared to other campaigns like the importance of donating blood, she says.

For example, there's a little boy right now in North Carolina named Thor Forte, who's 10 and has sickle cell disease. And he has been waiting for literally half his life, five years, for a donor to be available, Matchan says. He's a tough match, but they finally did find somebody. And then when the time came for the procedure, the person backed out. So two years later, the boy is still waiting.

Fortunately, quickly after finding out Mateo Goldman didnt match with anyone in his family, he was paired with a donor on the registry from Germany. Mandy Goldman says Laura Stterlin of Frankfurt was ready to go and donate, ultimately saving her son.

Mateo Goldman wrote Stterlin, whose name he did not know at the time, a thank you note reading: Dear Donor, thank you for giving me the bone marrow. You feel like youre already part of my family, he says.

And unlike usual Make-A-Wish requests, Mateo Goldman asked to meet Stterlin in person halfway across the world. The trip to Germany was planned for summer of 2020 but has since been canceled due to the pandemic.

In 2019 when she was reporting this story, Matchan had a trip planned to Germany. She ended up meeting Stterlin and hearing the story of how she became a donor. Stterlin said she was at a sporting event with her husband when she got hungry and went on the hunt for some grub.

Dear Donor, thank you for giving me the bone marrow. You feel like youre already part of my family.

Germany has a robust public service campaign to get citizens to donate bone marrow, Matchan says. So it came to no surprise to Stterlin when she came across a kiosk to sign up.

Just three months later, she got a call and an email from the registry saying that there is somebody in the United States for whom she could be a match and was asked if she would donate, Matchan says. A couple of days later, she went into the hospital and did the donation.

Stterlins stem cells then crossed the Atlantic Ocean, making their way to America during a snowstorm.

The cells started working in Mateo Goldman right away but not without some difficulties, Mandy Goldman says. He battled total body stiffness from graft-versus-host disease, a complication of the transplant.

But, you know, Matteo's an amazing kid, she says, so through it all, he was smiling and making the best of it, even though he was suffering for a lot of the time.

Two years later, in July of 2020, the cancer came back. But since Mateo Goldmans first transplant, the science had evolved greatly.

So much so that his older brother, Leo Goldman, became a candidate to donate his cells for the second stem cell transplant.

I didn't realize how I could get my brother's cells, Mateo Goldman, now 12 years old, says. Once that sank in, I felt that it would connect me and my brother more.

Right before Christmas last year, the family got extraordinary news: Mateo Goldman had zero cancer in his bone marrow, Mandy Goldman says.

Now the mom of four is on a mission to raise awareness on stem cell donations and share the story of how it saved her sons life.

The amazing feeling Leo got from being able to be the person who saved his brother's life is something he's going to carry with him forever, she says. And even Laura [Stterlin], she gave him three and a half years of his life that we get to spend with him. I just really want to educate people about how empowering it is to do something so incredible for somebody else.

When she started talking to others to raise awareness, she was shocked to discover how fearful people were in committing to be a donor.

If people could see the trauma these patients go through her son had a drain placed in his stomach, total body radiation, chemotherapy that left him head-to-toe in a skin-burning rash she says then maybe they wouldnt be scared to dedicate a small action for someone whose only cure is through a stem cell transplant.

Once people are educated about how much of a difference it makes, she says, then I feel like they would do it.

Click here to learn more about the Be The Match Registry.

Tinku Rayproduced and edited this interview for broadcast.Serena McMahonadapted it for the web.

Originally posted here:
After Bone Marrow Donation Saves 9-Year-Old Boy With Cancer, Boston Mom Fights To Raise Awareness - Here And Now

The outbreak of the Covidpandemic has made many patients reluctantto undergotreatments. While their apprehension seems to overpower them, doctors need to ensure thatstrict guidelines and protocols which assure the best quality service are followed.

Among elective surgeries andtransplants, bone marrow transplant cases have increased substantially in the past few months. Adhering to guidelines for pre-transplant evaluation and the management of a common complication, graft versus host disease (GVHD)is essential.

With the diversity of practice and expertise, the following guidelines will provide a pivotal tool for learning about the rapidly updated therapy landscape in Hematopoietic stem cell transplantation (HSCT).

The guidelines intended to provide a systematic approach for transplantation and help streamline clinical practices and educate new generations of physicians-in-training. Additionally, guidelines can help to evaluate a potential transplant recipient anddetermine if the patient is an eligible candidate for the procedure.

Types and selection of transplantation:

Selection of the type of transplantation for a patient depends on factors such as the type of malignancy, availability of a suitable donor, age of the recipient, the ability to collect a tumor-free autograft, the stage, the malignancy's susceptibility to the GVM effect, and status of disease -- bone marrow involvement, the bulk of disease, chemosensitivity to conventional chemotherapy. This method is particularly applicable for Autologous or Allogeneic Transplantation where one can have a sibling donor or a matched unrelated donor. In the case of a matched unrelated donor, ensure that the collection is adequate and stem cells are available well in time especially if they are imported from countries in Europe.

A haploidentical transplant is another type of transplant that uses healthy, blood-forming cells from a half-matched donor to replace the unhealthy ones. The ideal donor in this case is a family member.

That said, for bone marrow transplant blood products are the backbone and it is important to ensure to have adequate supply before you begin with the transplant.

What are the guidelines and protocols that can be adopted in current times?

Some measures for consideration are: Minimize face-to-face visits including monitoring and consider shifting to telehealth where feasible. Some adaptive community measures like the hospital in the home services, community practices for blood collection, imaging, and support services. For radiation oncology treatment, consider reducing fractions when supported by evidence Consider alternative and less resource-intensive treatment regimes. Minimize unnecessary visitors to cancer centers, for instance, limiting to only patients and their essential caregivers based on frailty and language needs Screen for possible symptoms of COVID-19 and triage patients for admission. If necessary, the admission has to be directed to oncology/hematology departments rather than emergency departments. Immunocompromised patients are likely to have atypical presentations of COVID-19 For suspected checkpoint inhibitor-related pneumonitis prioritizes COVID-19 testing for an early decision regarding corticosteroid therapy.

These are some guidelines that you should heed during a bone marrow transplant. While it is imperative to be updated about the guidelines, timely intervention can reduce the other possible complications during the process.

(The author is the Director, Medical Oncology and Hemato Oncology, atFortis Cancer Institute, Bangalore)

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Understanding bone marrow transplant: The guidelines and the protocols - The New Indian Express

Cynata Therapeutics (ASX: CYP), founded by two clever stem cell researchers and one wise Australian techpreneur, is in the process of developing a treatment for COVID-19.

Using its in-house stem cell technology Cymerus, the ASX-listed biotech hopes to treat one of the deadliest complications of COVID-19 -acute respiratory distress syndrome (ARDS).

In doing so Cynata would achieve what competitor Mesoblast (ASX: MSB) couldn't with FDA approval.

By deploying an industrialised approach to stem cell therapeutics, Cynata CEO Ross Macdonald (pictured) is confident the clinical trial process won't leave the company hamstrung.

In 1981 scientists discovered a way to derive embryonic stem cells from early mouse embryos.

The discovery thrilled scientists, and eventually led to the development of a method to do the same in lab-grown human embryos by 1998.

While there have been plenty of discussions surrounding the ethics of using of embryonic stem cells, these major scientific movements have pushed researchers to discover new and inventive ways of treating a whole raft of diseases and infections.

One such researcher, Dr Ian Dixon, saw potential for the use of mesenschymal stem cells (MSCs) - a type of stem cell that can differentiate into a variety of cell types enabling the treatment of many diseases and infections.

However there was still an obstacle to overcome: how do you mass produce enough cells needed to commercialise a treatment?

Luckily, two researchers at the University of Wisconson, Professor Igor Slukvin and Dr Maksym Vodyanik, had invented a biotechnological breakthrough called Cymerus.

The technology was able to do exactly what Dixon needed: the consistent manufacture of MSCs on an ultra-large scale; basically what Henry Ford did to the industrialisation of the auto industry, but for stem cells.

So in 2003 Dixon partnered with the two researchers to start Cynata - now an ASX-listed biotechnology company trialing a number of different treatments for a wide variety of ailments.

Most recently, Cynata's focus has been on developing a treatment for a complication of COVID-19 called acute respiratory distress syndrome (ARDS).

The complication ravages COVID-19 infected patients, destroying their organs through what is known as a cytokine storm. The complication is estimated to kill up to half of COVID-19 patients that suffer from it.

Melbourne-based Cynata is currently in the very early stages of its investigation into whether its MSCs will be able to treat the coronavirus complication overwhelming hospitals globally.

If this all sounds familiar, you might be thinking of another ASX-listed biotech called Mesoblast (ASX: MSB).

In March last year Mesoblast, also based in Melbourne, saw its shares surge after announcing plans to evaluate its stem cell treatment solutions on COVID-19 patients.

The group commenced the arduous clinical trial process to see if its remestemcel-L therapy could treat ARDS by using bone marrow aspirate from healthy donors - a similar approach the company had already taken to treat a condition many suffer from after receiving bone marrow transplants.

Mesoblast was riding high on the ASX following positive announcements surrounding the clinical traila process, especially back in April 2020 when a trial at New York City's Mt Sinai hospital found its remestemcel-L therpay achieved "remarkable" results.

Serious attention gathered around Mesoblast, with the company even securing $138 in funds from investors to continue its important research.

The company went so far as to sign a commercialisation deal for the COVID-19 treatment with Novartis, and the US Food and Drugs Administration (FDA) fast tracked the approvals process for the potential game-changing treatment.

However, in December 2020, Mesoblast hit a stumbling block.

Mesoblast's COVID-19 treatment flunked the test - its remestemcel-L therapy failed to show a lower mortality rate for patients in the prescribed 30-day timeframe of treatment.

At that point Cynata had commenced research into its own ARDS treatment. But did Mesoblast's failure unnerve Cynata CEO Ross Macdonald? Not a chance.

"I'm more confident that our trial will be successful where theirs was a failure," Macdonald said.

"If you use a process like we have developed - we don't rely on multiple different [stem cell] donations. You start with exactly the same material every time."

To explain, Macdonald used the analogy of a local caf; you normally expect a coffee from one caf to taste more or less exactly the same every time you go there - the same beans are used every time.

Whereas Macdonald said Mesoblast's process is like going to the same caf every day, but each visit they use different beans from a different supplier which leads to inconsistency in taste and flavour.

Cynata's approach with its MSCs is in line with the first example - what you get the first time from them will be replicated in each and every dose of the drug - while MSB's is like the latter.

"Yes, you still got the coffee, but the experience of the taste is totally different than it was yesterday," he said.

"The FDA said to Mesoblast, well you've got a manufacturing problem that is reliant upon multiple donors prepared to donate bone marrow and that is flawed.

"So with that in mind it's perhaps not surprising that they had a pretty disappointing result in the clinical trials."

Additionally, Macdonald said the initial investor reactions to MSB's early COVID-19 trail results were overblown.

"The initial data from their trial that got everybody excited was, in my view, quite flawed, because they said "look at how many patients are dying in intensive care units with COVID compared the patients that we treated," he said.

"But the reality of the situation was quite different. The control group at that time - the death rate was way, way higher than you would typically see for ARDS, whether its COVID or anything else. And it was simply because of the chaos that existed in intensive care units in New York in the first wave.

"So we think that the initial enthusiasm was perhaps a little misguided."

When asked why Mesoblast is receiving so much attention compared to Cynata, especially considering the above, Macdonald said it was simply because MSB is bigger and has been around for longer. For context, MSB has a market capitalisation of $1.46 billion, whereas Cynata's is just $94.56 million.

"I'd love to know why there is less attention, and how we can get our market cap above a billion dollars," joked Macdonald.

"I think the answer though is that they've been around for a lot longer than we have, they have spent a hell of a lot more money than we've spent - their monthly spend is more than we've spent for pretty much our entire existence.

"But I think the fundamental reason why is that data drives value in biotech, so the more clinical data you generate that shows your product works, the more attention you attract from investors."

That's not to say Cynata is being totally ignored in favour of the larger Mesoblast.

The company secured a $15 million placement led by $10 million from healthcare investor BioScience Managers in December.

The funds will be used to expand Cynata's clinical development pipeline and scale their operations in Australia.

As such, the company is preparing to expand its clinical development pipeline to include idiopathic pulmonary fibrosis, renal transplantation, and diabetic foot ulcers.

"So we're starting to garner that attention now that says two things - one, cell therapies are definitely a medical revolution and two, Cynata is part of that new generation of companies," Macdonald said.

As for the company's pipeline, in addition to the COVID treatment trials, Cynata is planning on launching three new clinical candidates that will get under way this year.

There's also Cynata's osteoarthritis trial, which Macdonald describes as significant for the biotech company; with 2 million patients in Australia and 30 million in the United States the company is hoping to tap into an $11 billion plus addressable market.

"It will ultimately show whether MSCs are useful in that particularly devastating condition," he said.

"It doesn't just affect people who want to go and play golf or tennis, it affects, particularly manual labourers who can no longer work.

"So the cost to the economy of osteoarthritis is quite significant, which is of course one of the reasons why the Australian Government is funding this trial."

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Why Cynata is hopeful its COVID treatment trial will succeed where others have failed - Business News Australia

Five years ago, I sat in a hospital lounge as a nurse laid out everything I as a caregiver would need to feed my husband intravenously: a bag of fluid called total parenteral nutrition, a vitamin solution, syringe, pump, a new 9-volt battery, a quarter for opening the battery chamber, and tiny alcohol wipes. She demonstrated the fussy, time-consuming process of hooking up the whole thing to my husbands central line.

Then she handed me a 20-page pamphlet detailing the procedure and I was on my own.

At the time, my husband, Brad, had been hospitalized for more than four months after a stem cell transplant that was plagued by complications for relapsed, aggressive lymphoma. He was unable to eat much by mouth, so he relied on IV nutrition, night after night, to survive at home.

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Over the years of Brads medical ordeal, I have administered IV antibiotics, flushed and sterilized port lines, checked blood sugar, given shots of Neulasta (a booster shot for immunity after chemotherapy), and much more. My shock and anger at suddenly being expected to be a bedside nurse faded, and handling needles and central lines became routine.

Brad no longer needs this level of care, but his immune system is still suppressed and he is chronically ill. Were now mired in the long wait for Covid-19 vaccines which, in my state, California, could take several confusing, frustrating months.

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The Covid-19 vaccines are miracles of fast-moving science, but Covid-19 vaccination has so far been a slow grind. With daily deaths in the U.S. continuing to number in the thousands and the country barreling toward the devastating figure of half a million deaths, we need all hands on deck to turn vaccines into vaccinations.

The gigantic systems that must figure out how to get shots into arms U.S. health care and the federal government are better known for ponderous bureaucracy than nimble pivots and stopgap solutions. As Ive watched the delays, Ive thought often of the times I was deputized to give my husband care during the medical ordeal that left him chronically ill.

I could give him the shot, I keep thinking.

Every day, family caregivers like me, with no medical experience, volunteer or are voluntold to provide care that a generation or two ago would have been administered only by a nurse. According to a 2020 AARP survey, there are more than 50 million family caregivers in the U.S. We represent a resource that, if deployed, could help get vaccines into arms, the well-known last mile problem.

In some ways, caregivers have been sidelined during the pandemic. Because of justified concerns about infection, hospitals have had to ban family caregivers from hospital visits. When we went on lockdown, I worried about my husbands immune suppression, but briefly consoled myself with the idea that if he did get sick, I would know how to advocate and care for him, given my prior experience. Then I soon realized I wouldnt even get in the door.

Of course, the slow pace of vaccination has many causes: dose shortages, the negligence of the Trump administration, the ethical questions surrounding who to prioritize, and personnel shortages.

What if the valuable experience of each and every caregiver could be applied to the most critical effort of this moment, vaccination?

Caregivers, many of us already trained in basic at-home care and used to cutting through health-care bureaucracy, could pitch in to speed up vaccinations. Deputizing caregivers to give shots at home could ease the enormous, yearlong strain on the medical and public health systems while also providing a safer, more accessible vaccination method for vulnerable seniors, those with limited mobility, and immune-compromised people like my husband, who shouldnt be waiting for hours in mass clinics.

The Biden administrations strategic plan to combat the pandemic promises federal leadership and faster action on vaccination nationwide, bringing much-needed hope in a dark time. Reports indicate the administration will deploy the National Guard and the Federal Emergency Management Agency to aid the effort.

I hope it will also explore tapping ordinary citizens. In addition to finding ways to use caregivers, we should consider mass volunteer efforts for both direct care and support. The United Kingdom, for instance, started a volunteer corps in which not only retired doctors but also teachers and other laypeople are giving shots. In Connecticut and Alberta, veterinarians have been deputized. Its time to extend such efforts more broadly.

Vaccination campaigns in regions beset by childhood diseases have long relied heavily on volunteers for last-mile delivery. My sister-in-law recently told me that, at age 17, she went on a volunteer summer program to vaccinate kids in Ecuador. She and her fellow teens practiced, first on oranges and then on each other, with syringes filled with saline. Im not proposing we send out needle-wielding minors, even in a crisis as deep as the present one, but the moment cries out for innovative solutions.

Both the individual family care I am expected to provide for my husband and the broad tragedies of the pandemic reflect the profound strains on American health care. But shifting higher-level care tasks to family caregivers, hard though it is on individuals, represents innovation a workaround to save lives despite systemic challenges and has given millions of Americans experience that could help meet the moment.

With the availability of Covid-19 vaccines, the end of the pandemic is tantalizingly close. Lets use every resource we have to get there, including an often-overlooked one: caregivers.

Kate Washington, a journalist based in Sacramento, Calif., is the author of Already Toast: Caregiving and Burnout in America (Beacon Press, March 2021).

Read this article:
Mobilize family caregivers to speed the rollout of Covid-19 vaccines - STAT

People living with cancerincluding those undergoing treatmentshould receive COVID-19 vaccines as soon as they are available, according to new guidelines from the National Comprehensive Cancer Network (NCCN).

While people with some types of cancer and those receiving certain cancer treatments may not respond quite as well, the vaccines should still provide partial protection, which is especially important because some cancer patients are at higher risk for COVID-19 complications.

Right now, there is urgent need and limited data, said committee co-leader Steve Pergam, MD, MPH,of the Seattle Cancer Care Alliance and the Fred Hutchinson Cancer Research Center, headquarters of the National Institutes of Healths COVID-19 Prevention Network. Our number one goal is helping to get the vaccine to as many people as we can. That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19. The evidence we have shows that people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.

Much remains to be learned about COVID-19 in people with cancer. Studies have shown that people with blood cancers like leukemia or lymphoma and lung cancer are at greater risk for severe COVID-19 and death, but those with other types, such as breast or lung cancer, do not appear to be at higher risk. Patients with active or advanced cancer are likely to fare worse. Although studies of the effects of cancer treatment on COVID-19 outcomes have yielded conflicting results, therapies that cause immune suppression seem to lead to poorer outcomes.

Two mRNA vaccines from Pfizer/BioNTech and Moderna were authorized by the Food and Drug Administration in December. These vaccines were 95% and 94% effective for preventing symptomatic COVID-19 in Phase III clinical trials. Vaccine candidates from AstraZeneca, Johnson and Johnson and Novavax are also effective, especially for preventing severe disease, and are likely to receive emergency use authorization in the coming months. All the vaccines were shown to be safe.

A Centers for Disease Control and Prevention (CDC) advisory committee developed a vaccine prioritization plan that puthealth care workers and residents of long-term care facilitiesfirst in line, followed bypeople overage 75 and certain frontline essential workers. The CDC later expanded eligibility to include everyone over 65 and people with underlying health conditionsincluding cancerthat put them at risk for more severe COVID-19. But current supplies are nowhere near adequate to vaccinate everyone whos eligible.

The NCCNs COVID-19 Vaccine Committee, which includes top hematology and oncology experts in the areas of infectious diseases, vaccine development and delivery, medical ethics and health information technology, recommends that all people with cancer should get a vaccine. The committee also advises that caregivers and people living in the same household with cancer patients should also get vaccinated when they are eligible.

While clinical trials have shown that the vaccines are highly effective at reducing the risk of becoming ill with COVID-19, it is still not clear how well they prevent asymptomatic infection and transmission, so the committee emphasizes the importance of continuing to follow precautions such as wearing masks and social distancing.

Although people on cancer treatment were excluded from the COVID-19 vaccine trials, experts say theres no reason to think the vaccines wont be safe for this group. The currently authorized vaccines do not contain live virus and therefore cannot cause disease, even in immunocompromised people.

The data we have on these vaccines shows theyre remarkably safe in the general population based on the trials. Admittedly, very few patients with active cancer or in active therapy were included in the trials. But having gone through all the documentation for both of these vaccines, it looks remarkably safe, Gary Lyman, MD, of Fred Hutch, who helped start the COVID-19 and Cancer Consortium, told the Fred Hutch News Service. I have no real concerns that there will be big surprises when it comes to safety for the cancer patient population. The risk to these patients from COVID is high and the risks from the vaccines appear very low.

While the vaccines appear safe for people with cancer, some patients may not respond as well, particularly those whose cancer or treatment causes immune suppression. Some blood cancers affect B cells, the white blood cells that produce antibodiesa key player in vaccine response. Chemotherapy and radiation can deplete white blood cells, and people undergoing stem cell transplants or receiving CAR-T therapy have their own immune cells killed off with chemo or radiation to make room for the new cells.

The NCCN committee recommends that people receiving intensive chemotherapy for leukemia should wait to be vaccinated until their white blood cell count recovers. Stem cell transplant and CAR-T recipients should delay vaccination until three months after the procedure to improved the chances that the vaccine will produce a good immune response. People undergoing major surgery should wait at least a few days. But everyone elseincluding patients receiving chemotherapy for solid tumors, targeted therapy, immunotherapy or radiation therapyshould get a vaccine as soon as they can.

If it is necessary to prioritize among people with cancer, the committee recommends moving those on active treatment (except those taking only hormone therapy), those who plan to start treatment soon and those who have recently finished treatment to the front of the line. Cancer patients with other risk factors, including older age and additional health conditions, should also be prioritized.

Finally, the guidance acknowledges the disparities and social inequities related to COVID-19Black and Latino people are more likely to be exposed to the coronavirus and more likely to develop severe disease and die from it, but are less likely to get vaccinated.

One of our primary goals is reducing morbidity and mortality, saidSirisha Narayana, MD,chair of the University of California at San Francisco Ethics Committee. We also have to take social determinants of health into account and make special efforts for people in high-risk communities.

The medical community is rising to one of the biggest challenges we have ever faced, addedNCCN CEO Robert Carlson, MD. The COVID-19 vaccines exemplify the heights of scientific achievement. Now we have to distribute them quickly, equitably, safely and efficiently, using clearly defined and transparent principles.

Given their higher risk for COVID-19, the NCCN, the American Society of Clinical Oncology and other advocates are asking that people with cancer be given priority for vaccination.

People with metastatic and active cancers die at a rate similar to people over age 75; if we die at the rate of 75 year olds we should be vaccinated with the 75 year olds, Kelly Shanahan, an advocate living with metastatic breast cancer, told Cancer Health. Those of us with active and metastatic cancers dont have the luxury of just staying home. We must get our treatments and scans and see our oncologists. Keep us out of the hospitalsand morguesby prioritizing us for the COVID19 vaccinations!

Click here to read the full NCCN COVID-19 vaccine guidance.

Click here for more news about COVID-19.For more, visit our sister site, COVID Health.com.

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People With Cancer Should Receive COVID-19 Vaccine, Experts Say - Cancer Health Treatment News

DGAP-News: Evotec SE / Key word(s): Miscellaneous04.02.2021 / 07:30 The issuer is solely responsible for the content of this announcement.

Hamburg, Germany, 04 February, 2021:Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) today announced that the Company has entered into a multi-year partnership with the Medical Center Hamburg-Eppendorf ("UKE") for the development of a highly innovative first-in-class cell therapy approach for the treatment of heart failure.

Under the terms of the partnership, Evotec and UKE will leverage their complementary strengths for the development of a new cell therapy approach using Engineered Heart Tissue for the treatment of heart failure. Heart failure is frequently associated with ischemic heart disease and often comes with a poor prognosis. Mortality is comparable to that of the most common cancers, with <50% 4-year survival. Treatment of patients suffering from heart failure is expected to deliver significant patient benefit through improved heart function, ultimately leading to an improved prognosis.

Evotec leverages its industry-leading human induced pluripotent stem cells ("hiPSCs") platform to establish GMP-compatible process development and upscaling for large-scale generation of clinical-grade heart muscle cells known as cardiomyocytes. Evotec will also contribute genetically modified GMP iPSC lines, which contain alterations preventing rejection of the cardiomyocyte-containing product by patient immune systems ("cloaking"), and include additional safety mechanisms to control unwanted proliferation of graft cells. By using these GMP-grade iPSC lines, the project will deliver off-the-shelf products, which can be implanted in broad patient populations with little to no immunosuppression. UKE applies its proprietary Giga Patch Method for the generation of fully functional heart tissue suitable for cardiac transplantation. Further in vivo validation and development activities will be shared jointly between the partners. Evotec will be responsible for GMP and pre-clinical activities as well as for any subsequent partnering of the programme.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: "We are very excited about this collaboration with the UKE. Both Evotec and UKE have developed and refined their respective technology platforms over a number of years and have now decided to jointly drive this cardiac cell therapy programme towards clinical development. We are confident that this partnership will deliver a new therapeutic option for patients who suffer from heart failure."

Prof. Dr Thomas Eschenhagen, Director of the Institute of Experimental Pharmacology and Toxicology at UKE, added: "We are excited about the new opportunities the partnership with Evotec will create. After having worked on means to repair injured heart by 3-dimensional heart muscle patches for over two decades, joining forces with Evotec and its industrialized hiPSC platform and new cell lines, will bring this development to a new stage. We are aiming at the most efficient and safest therapy in the field."

"We are very happy to see a scientific success story advance to a feat of technology transfer. Translation of scientific insights into therapeutic options is a key mission of our University Medical Center", says Prof. Dr Blanche Schwappach-Pignataro, the Dean of Faculty of Medicine of the UKE.

No financial terms of the agreement were disclosed.

About heart failureHeart failure is a severe global health burden with more than 26 million people suffering with the condition worldwide, disproportionately affecting elderly people. While there are options to treat heart failure both medicinally and with devices, there is currently no treatment that targets the cause of the disease or significantly slows down its progression.

About Evotec and iPSCInduced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from adult cells. Pluripotent stem cells hold great promise in the field of regenerative medicine. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease.

Evotec has built an industrialised iPSC infrastructure that represents one of the largest and most sophisticated iPSC platforms in the industry. Evotec's iPSC platform has been developed over the last years with the goal to industrialise iPSC-based drug screening in terms of throughput, reproducibility and robustness to reach the highest industrial standards, and to use iPSC-based cells in cell therapy approaches via the Company's proprietary EVOcells platform.

ABOUT THE MEDICAL CENTER HAMBURG-EPPENDORF (UKE)Since its foundation in 1889, the Medical Center Hamburg-Eppendorf (UKE) has been one of the leading clinics in Europe. With about 13,600 employees, the UKE is one of the largest employers in Hamburg. Each year, the UKE treats around 511,000 patients, 106,000 of whom are inpatients and 405,000 outpatients. The emphasis in UKE's research are the neurosciences, cardiovascular research, care research, oncology, as well as infections and inflammations. Other potential areas of the UKE are molecular imaging and skeletal biology research. The UKE trains about 3,400 medical specialists and dentists.Knowledge, Research, Healing through Shared Competence: The UKE | http://www.uke.de

ABOUT EVOTEC SEEvotec is a drug discovery alliance and development partnership company focused on rapidly progressing innovative product approaches with leading pharmaceutical and biotechnology companies, academics, patient advocacy groups and venture capitalists. We operate worldwide and our more than 3,500 employees provide the highest quality stand-alone and integrated drug discovery and development solutions. We cover all activities from target-to-clinic to meet the industry's need for innovation and efficiency in drug discovery and development (EVT Execute). The Company has established a unique position by assembling top-class scientific experts and integrating state-of-the-art technologies as well as substantial experience and expertise in key therapeutic areas including neuronal diseases, diabetes and complications of diabetes, pain and inflammation, oncology, infectious diseases, respiratory diseases, fibrosis, rare diseases and women's health. On this basis, Evotec has built a broad and deep pipeline of more than 100 co-owned product opportunities at clinical, pre-clinical and discovery stages (EVT Innovate). Evotec has established multiple long-term alliances with partners including Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CHDI, Novartis, Novo Nordisk, Pfizer, Sanofi, Takeda, UCB and others. For additional information please go to http://www.evotec.com and follow us on Twitter @Evotec.

FORWARD-LOOKING STATEMENTSInformation set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgement of Evotec as of the date of this press release. Such forward-looking statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.

Media Contact Evotec SE:Gabriele Hansen, SVP Head of Global Corporate Communications & Marketing, Phone: +49.(0)40.56081-255, gabriele.hansen@evotec.com

IR Contact Evotec SE:Volker Braun, SVP Head of Global Investor Relations & ESG, Phone: +49.(0)40.56081-775, volker.braun@evotec.com

04.02.2021 Dissemination of a Corporate News, transmitted by DGAP - a service of EQS Group AG.The issuer is solely responsible for the content of this announcement.

The DGAP Distribution Services include Regulatory Announcements, Financial/Corporate News and Press Releases. Archive at http://www.dgap.de

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Evotec and Medical Center Hamburg-Eppendorf Enter Partnership to Develop iPSC-Based Tissue Therapy f - PharmiWeb.com

29 Jan 2021

Part 2 of a two-part series. Click here for Part 1.It turns out a persons risk associated with ApoE4 goes beyond Alzheimers and vascular disease. This apolipoprotein allele can also worsen infections caused by certain viruses. One of those appears to be SARS-CoV-2, the cause of COVID-19, according to two epidemiological studies. In the January 11 Gerontology, researchers led by Miguel Calero, Queen Sofia Foundation Alzheimer Research Center, Madrid, Spain, reported that aged ApoE4 carriers are more likely to show COVID-19 symptoms than ApoE3 carriers. This supports a paper in the September 16, 2020, Journals of Gerontology. Researchers led by David Melzer, University of Exeter, England, U.K., reported that older ApoE4 carriers are more likely to test positive for the virus and more likely to die from COVID-19 than are ApoE3s carriers. Why might this be?

In the January 4 Cell Stem Cell, researchers led by Yanhong Shi, Beckman Research Institute, Duarte, California, and Vaithilingaraja Arumugaswami, University of California, Los Angeles, reported that the new coronavirus infected more ApoE4 neurons and astrocytes than their ApoE3 counterparts in cell culture. Astrocytes stoked the fire, upping the number of infected cells in co-cultures and in astrocyte-containing brain organoids. Infected neurons degenerated, while astrocytes swelled and their nuclei broke apart. Though this may not explain why ApoE4 carriers are at higher risk of COVID-19, it suggests that they may be more prone to long-term neurological symptoms of the disease (see Part 1 of this series).

To probe how various factors, including ApoE genotype, affect the severity of a persons COVID-19, Calero and colleagues phoned people ages 75-94 who, as part of in the Vallecas Project in Madrid, had been genotyped for ApoE. From 20112013, this observational cohort study tracked markers that might predict future dementia (Olarzaran et al., 2015).In April 2020, first author Teodoro del Ser Claero asked Vallecas participants if they had any COVID-19 symptoms, and learned that ApoE4 carriers were 2.4 times as likely to reply in the affirmative, and to have had a COVID-19 diagnosis.

This aligns with Melzer and colleagues data. They sifted through the U.K. Biobank database, which now includes COVID-19 infection data. First author Chia-Ling Kuo stratified participants based on APOE genotype. ApoE4/4 carriers were 2.2 times as likely to have tested positive or have had severe disease, and 4.3 times as likely to have died from COVID-19 than were ApoE3/3s. These differences remained even after the researchers corrected for comorbidities known to worsen COVID-19, such as dementia, hypertension, and Type 2 diabetes.

Even so, Caleb Finch, University of Southern California, Los Angeles, and Alexander Kulminski, Duke University, Durham, North Carolina, think the comorbidities may explain the association. ApoE cluster haplotypes associate with the same morbidities from cardiovascular disease and obesity that increase vulnerability to COVID-19, they note in a review in the same journal. The ApoE locus was first recognized as a genetic determinant of cardiovascular disease in the 1980s, through its effect on blood lipid and cholesterol levels (Sing et al., 1985). Some research even indicated ApoE4 protected people from lipophilic pathogens (Martin, 1999). But at least for COVID, the latest data suggest the opposite. The ApoE trail, like a Moebius strip, takes us back to where we started from, four decades ago, with another view, wrote Finch and Kulminski. To understand how ApoE4 may increase COVID-19 infectivity and mortality, we have returned to the original associations of ApoE variants with blood lipids, vascular disease, and cognition.

Zooming in to the cellular level may provide insight on how ApoE4 renders cells more susceptible to viruses. For example, HIV more easily penetrates human cells if they are ApoE4/4 (Burt et al., 2008). In mice, herpes simplex virus (HSV) exploits the lipoprotein to enter brain cells, leading to a higher viral burden in ApoE4 than ApoE3 transgenic mice (Burgos et al., 2006). What about SARS-CoV-2?

ApoE4 Worsens SARS-CoV-2 Damage. The virus infected neurons and astrocytes in cell culture and brain organoids. ApoE4 cells fared worse, remdesivir protected them. [Courtesy of Wang et al., Cell Stem Cell, 2021.]

Shi wondered if ApoE4 could explain the neurological effects of SARS-CoV-2 in some people. To begin with, co-first authors Cheng Wang, Mingzi Zhang, and colleagues confirmed the virus penchant for certain brain cells (see Part 1 of this series). They differentiated human induced pluripotent stem cells (hiPSCs) into neuronal progenitors (NPCs), neurons, astrocytes, oligodendrocyte progenitor, or brain endothelial cells, then infected them with SARS-CoV-2. Immunostaining detected the viral spike protein in less than 5 percent of NPCs, neurons, and astrocytes, which Shi called a low-grade infection. The virus also infected 60-day-old brain organoids comprising NPCs and neurons.

Astrocytes are known to spread neurotropic viruses in the CNS, including Japanese encephalitis, West Nile, and Zika viruses (Soung et al., 2018; Potokar et al., 2019). Could astrocytes stoke the COVID fire in neurons and organoids? Indeed, more neurons tested positive for SARS-CoV-2 spike protein in neuron-astrocyte co-cultures than in monoculture. The scientists also saw higher viral RNA loads in neurons from organoids that had incorporated astrocytes than in those that did not.

Wang, Zhang, and colleagues then homed in on APOE genotype. They used CRISPR/Cas9 to create isogenic cell lines from iPSCs taken from ApoE3/3 and ApoE4/4 donors. They differentiated the cells into neurons and co-cultured them with ApoE3 astrocytes for three weeks. Then they added SARS-CoV-2, using one viral particle per cell. Immunostaining revealed spike protein in all neurons within 24 hours. After 72 hours, the viral protein content in all neurons had grown, but E4 neurons had 1.5 times more than E3 neurons (see image below).

Viral Invasion. After SARS-Cov-2 infects neurons (purple, left panels), its spike protein (green) popped up within 24 hours (middle) and accumulated over 72 hours (right panel). Infected ApoE4 neurons (bottom) had more viral protein than isogenic ApoE3 lines (top). [Courtesy of Wang et al., Cell Stem Cell, 2021.]

At that point, infected cells formed fewer neurites than did uninfected cells, and the neurites were short. Infected ApoE4 cells had even fewer neurites than ApoE3 cells, and they were shorter still. Staining with Syn 1 revealed fewer synapses in both infected neurons.

What about astrocytes? More iPSC-derived ApoE4/4 astrocytes were infected than iPSC-derived ApoE3/3 cells. The former had fatter somas, longer processes, and nuclei that were more fragmented compared to infected ApoE3 cells (see image below). Taken together, these findings hint at an ApoE-dependent reaction to viral infection, with ApoE4 neurons and astrocytes more severely damaged.

Angrier Astrocytes. SARS-CoV-2-infected (red) E4 astrocyte soma (right four panels) had fragmented nuclei (blue) and grew fatter (green) than E3 astrocyte soma (left four panels) whose nuclei remained intact. [Courtesy of Wang et al., Cell Stem Cell, 2021.]

Why were E4 astrocytes worse off than the E3 cells? Jessica Young, University of Washington, Seattle, thinks it may have to do with endosomes. Of 40 genes previously identified as crucial for SARS-CoV-2 infection, two, the endosomal entry receptor ACTR2 and the ATP6AP2 ATPase, are involved in endosome function (Daniloski et al., 2021). Both are more highly expressed in ApoE4 astrocytes, which have larger early endosomes than do E3 cells (Oct 2020 news). Proteins involved in endosomal entry and transport are more abundant in APOE4 cells, which may facilitate the cellular infectivity of the virus, Young told Alzforum (full comment below). G. William Rebeck, Georgetown University, Washington, D.C., agreed the endosome might be involved. The speculation that these ApoE effects may be due to differentially expressed genes related to endosomal trafficking builds on a model that has been developed across several labs over the past two decades. (Full comment below.)

The FDA-approved drug remdesivir quelled SARS-CoV-2 infection in cultured neurons and astrocytes. When Wang, Zhang, and colleagues pretreated cells with 10 M remdesivir two hours before adding the virus, fewer neurons and astrocytes became infected. The drug also bumped up the number and length of neurites and reduced the number of fragmented nuclei in infected astrocytes compared to vehicle treatment.

Whether this remdesivir is relevant in the clinic remain to be seen. Remdesivir is thought to poorly enter the brain, Rik van der Kant, Vrije Universiteit Amsterdam, and Diederik van de Beek, Amsterdam UMC, wrote in a joint comment (below). David Clifford, Washington University, St. Louis, cautioned against overinterpreting these results based on what he hears from fellow clinicians who are treating COVID-19 patients. Clinically, remdesivir appears minimally effective and is increasingly considered unimportant in COVID-19 patient care, he wrote. Treating the CNS is always more challenging than treating peripheral infections.Chelsea Weidman Burke

Originally posted here:
APOE Tied to Increased Susceptibility to SARS-CoV-2 | ALZFORUM - Alzforum

Are there updated data for LIBTAYO in advanced CSCC? What do they show?

Longer-term data from EMPOWER-CSCC-1 were presented at the 2020 American Society of Clinical Oncology (ASCO) virtual meeting. These results showed an ORR of 46% (95% CI: 39%-53%) following treatment with LIBTAYO, with a median time to response of 2 months (interquartile range: 2-4 months) across the three treatment groups, which were metastatic CSCC and locally advanced CSCC dosed at 3mg/kg every 2 weeks and metastatic CSCC dosed at 350mg every 3 weeks. The median time to CR was 11 months (interquartile range: 7.4-14.8months) among those who achieved a CR in any group. The median DoR hadyet to be reached for any treatment group (range for groups combined: 1.9-34.3 months).4,10

Updated response rates arein the table below.4,10

Safety was generally consistent with previous data. The most common adverse reactions reported were fatigue (35%), diarrhea (28%) and nausea (24%). The most common Grade 3 or higher adverse reactions were pneumonitis (3%), autoimmune hepatitis (2%), anemia, colitis and diarrhea (each 1%).

Warnings and Precautions

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue at any time after starting treatment. While immune-mediated adverse reactions usually occur during treatment, they can also occur after discontinuation. Immune-mediated adverse reactions affecting more than one body system can occur simultaneously. Early identification and management are essential to ensuring safe use of PD-1/PD-L1 blocking antibodies. The definition of immune-mediated adverse reactions included the required use of systemic corticosteroids or other immunosuppressants and the absence of a clear alternate etiology. Monitor closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

No dose reduction for LIBTAYO is recommended. In general, withhold LIBTAYO for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue LIBTAYO for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated adverse reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.

Withhold or permanently discontinue LIBTAYO depending on severity. In general, if LIBTAYO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids.

Immune-mediated pneumonitis:LIBTAYO can cause immune-mediated pneumonitis. In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.7% (22/591) of patients receiving LIBTAYO, including fatal (0.3%), Grade 4 (0.3%), Grade 3 (1.0%), and Grade 2 (1.9%). Pneumonitis led to permanent discontinuation in 1.9% of patients and withholding of LIBTAYO in 1.9% of patients. Systemic corticosteroids were required in all patients with pneumonitis. Pneumonitis resolved in 59% of the 22 patients. Of the 11 patients in whom LIBTAYO was withheld, 7 reinitiated after symptom improvement; of these 1/7 (14%) had recurrence of pneumonitis. Withhold LIBTAYO for Grade 2, and permanently discontinue for Grade 3 or 4. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids.

Immune-mediated colitis: LIBTAYO can cause immune-mediated colitis. The primary component of immune-mediated colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1 blocking antibodies. In cases of corticosteroid-refractory immune-mediated colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.2% (7/591) of patients receiving LIBTAYO, including Grade 3 (0.3%) and Grade 2 (0.7%). Colitis led to permanent discontinuation in 0.2% of patients and withholding of LIBTAYO in 0.7% of patients. Systemic corticosteroids were required in all patients with colitis. Colitis resolved in 71% of the 7 patients. Of the 4 patients in whom LIBTAYO was withheld, none reinitiated LIBTAYO. Withhold LIBTAYO for Grade 2 or 3, and permanently discontinue for Grade 4. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids.

Immune-mediated hepatitis:LIBTAYO can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 1.9% (11/591) of patients receiving LIBTAYO, including fatal (0.2%), Grade 4 (0.2%), and Grade 3 (1.5%). Hepatitis led to permanent discontinuation of LIBTAYO in 0.8% of patients and withholding of LIBTAYO in 0.8% of patients. Systemic corticosteroids were required in all patients with hepatitis. Additional immunosuppression with mycophenolate was required in 9% (1/11) of these patients. Hepatitis resolved in 64% of the 11 patients. Of the 5 patients in whom LIBTAYO was withheld, none reinitiated LIBTAYO.

For hepatitis with no tumor involvement of the liver: Withhold LIBTAYO if AST or ALT increases to more than 3 and up to 8 times the upper limit of normal (ULN) or if total bilirubin increases to more than 1.5 and up to 3 times the ULN. Permanently discontinue LIBTAYO if AST or ALT increases to more than 8 times the ULN or total bilirubin increases to more than 3 times the ULN.

For hepatitis with tumor involvement of the liver: Withhold LIBTAYO if baseline AST or ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULN. Also, withhold LIBTAYO if baseline AST or ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN. Permanently discontinue LIBTAYO if AST or ALT increases to more than 10 times ULN or if total bilirubin increases to more than 3 times ULN. If AST and ALT are less than or equal to ULN at baseline, withhold or permanently discontinue LIBTAYO based on recommendations for hepatitis with no liver involvement.

Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids.

Immune-mediated endocrinopathies: For Grade 3 or 4 endocrinopathies, withhold until clinically stable or permanently discontinue depending on severity.

Immune-mediated nephritis with renal dysfunction: LIBTAYO can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.5% (3/591) of patients receiving LIBTAYO, including Grade 3 (0.3%) and Grade 2 (0.2%). Nephritis led to permanent discontinuation in 0.2% of patients and withholding of LIBTAYO in 0.3% of patients. Systemic corticosteroids were required in all patients with nephritis. Nephritis resolved in all 3 patients. Of the 2 patients in whom LIBTAYO was withheld, none reinitiated LIBTAYO. Withhold LIBTAYO for Grade 2 or 3 increased blood creatinine, and permanently discontinue for Grade 4 increased blood creatinine. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids.

Immune-mediated dermatologic adverse reactions: LIBTAYO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Immune-mediated dermatologic adverse reactions occurred in 2.0% (12/591) of patients receiving LIBTAYO, including Grade 3 (1.0%) and Grade 2 (0.8%). Immune-mediated dermatologic adverse reactions led to permanent discontinuation in 0.3% of patients and withholding of LIBTAYO in 1.4% of patients. Systemic corticosteroids were required in all patients with immune-mediated dermatologic adverse reactions. Immune-mediated dermatologic adverse reactions resolved in 42% of the 12 patients. Of the 8 patients in whom LIBTAYO was withheld for dermatologic adverse reaction, 5 reinitiated LIBTAYO after symptom improvement; of these 60% (3/5) had recurrence of the dermatologic adverse reaction. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold LIBTAYO for suspected SJS, TEN, or DRESS. Permanently discontinue LIBTAYO for confirmed SJS, TEN, or DRESS. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids.

Other immune-mediated adverse reactions: The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% in 591 patients who received LIBTAYO or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions.

Infusion-related reactions

Severe infusion-related reactions (Grade 3) occurred in 0.2% of patients receiving LIBTAYO. Monitor patients for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or 2, and permanently discontinue for Grade 3 or 4.

Complications of Allogeneic HSCT

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT.

Embryo-fetal toxicity

LIBTAYO can cause fetal harm when administered to a pregnant woman due to an increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LIBTAYO and for at least 4 months after the last dose.

Adverse reactions

Use in specific populations

Please click here for full Prescribing Information.

INDICATIONAND USAGE

LIBTAYO is indicated for the treatment of patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation.

++++

References:

1. LIBTAYO (cemiplimab-rwlc) injection full U.S. prescribing information. Regeneron Pharmaceuticals, Inc., and sanofi-aventis U.S. LLC. Available at: https://www.regeneron.com/sites/default/files/Libtayo_FPI.pdf

2. Mansouri B, Housewright C. The treatment of actinic keratosesthe rule rather than the exception. J Am Acad Dermatol 2017; 153(11):1200. doi:10.1001/jamadermatol.2017.3395.

3.Schmults CD, et al. High-Risk Cutaneous Squamous Cell Carcinoma A Practical Guide for Patient Management. Springer. ISBN 978-3-662-47081-7 (eBook).DOI 10.1007/978-3-662-47081-7.

4. Data on File. Regeneron Pharmaceuticals Inc. 2020.

5. Data on File. Regeneron Pharmaceuticals Inc. 2018.

6. Migden M, Rischin D, Schmults C, Guminski A, Hauschild A, Lewis K et al. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. New England Journal of Medicine. 2018;379(4):341-351.

7. NCCNClinical Practice Guidelines in Oncology (NCCN Guidelines) forSquamous Cell Skin Cancer V.2.2020. National Comprehensive CancerNetwork, Inc. 2020.

8. Califano JA, Lydiatt WM, Nehal KS, et al. Cutaneous squamous cell carcinoma of the head and neck. In: Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th ed. Springer; 2017:171-181.

9. Jennings L, Schmults CD. Management of high-risk cutaneous squamous cell carcinoma. J Clin Aesthet Dermatol. 2010;3(4):39-48.

10. RischinD, Khushalani NI, Schmults CD, et al. Phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC): longer follow-up. Poster presented at: American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program; May 29-31, 2020.

LIB.20.04.0063 1/21

Read more:
Transforming Outcomes in Advanced CSCC with Immunotherapy - LWW Journals

ASHLEY Cain praised his sick daughter for 'smiling everyday' as she battles leukaemia.

The former footballer's baby daughter Azaylia underwent a stem cell transplant 10 days ago after her leukaemia had returned.

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He told The Sun that four-month old is at high risk of complications and that the transplant has likely a lower success outcome after her leukaemia returned.

But he has since opened up about how the tot is doing after the transplant, admitting Azaylia was in a lot of pain.

Taking to Instagram to share some adorable pictures of his smiling daughter, Ashley let his fans know how was she was going.

He captioned the series of pics: "It has now been 10 days since Azaylias Stem Cell transplant and she still gives Daddy bright eyes and big smiles everyday despite her pain to help me through my worries. "

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"She is going through quite some pain at the moment and has ran into a few side effects over the last 10 days.

Ashley added: "But, she is doing well and her love for life seems to outshine any trouble she is going through. She is a remarkable little girl and her strength fuels my soul every single day!

"LETS GO CHAMP! I BELIVE IN YOU! "

His fans rushed to send words of encouragement to him, Azaylia and his partner, Safiyya Vorajee.

9

"Keep going champs," wrote model, Brandon Myers.

MMA fighter Kane Mousah wrote: "Shes Amazing Brother Shes Has Got This LETS GO CHAMP !!! "

Another Instagram user wrote: "What an inspirational little baby girl you have ! Strongest human Ive known yet ... just an inspiring family all in all."

Azaylia had undergone a second round of chemotherapy to clear the cancer ahead of the stem cell transplant.

However doctors informed the couple that despite their best efforts, the leukaemia had returned quickly.

9

Azaylia, who is battling the rarest form of the disease, will undergo the transplant tomorrow at Birmingham Childrens Hospital.

Speaking to The Sun, Ashley, 30, explained: All we wanted for Christmas was a match for our daughter. We have been told that we have found a match for our daughter. It is amazing. We have had our routes of ups and downs and this is the next stage."

Ashley and Safiyya have been staying at in theHoliday Inn at Snow Hill, next to the hospital, to be close to Azaylia at all times.

9

Speaking ahead of the transplant, Ashley said the news Azaylias leukaemia had returned was hard to comprehend.

He said: It came as a massive blow to us and brought us to our knees. It means she will have to go into transplant with Leukaemia which is not ideal at all.

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We were told that because of her age and the aggressiveness of her leukaemia she is in the high risk category for transplant complications and the poor risk category for transplant success.

This news was incredibly hard to hear and has made every day even more difficult to face since.

Ashley said: Were remaining strong and positive for our daughter, she has got past the first stage of treatment against the odds and we truly believe that she will do the same this time around.

She is a fighter, she is a warrior and she will do this and we will be by her side every step of the way!

Read more here:
Ashley Cain is living his worst nightmare as his baby daughter battles leukaemia in hospital - The Sun

Autologous Stem Cell and Non Stem Based therapies Market delivers a succinct analysis of industry size, regional growth and revenue forecasts for the upcoming years. The report further sheds light on significant challenges and the latest growth strategies adopted by manufacturers who are a part of the competitive spectrum of this business domain.

Autologous Stem Cell and Non Stem Based therapies Market: Global Size, Trends, Competitive, Historical & Forecast Analysis, 2021-2027. Rise in the prevalence of Cancer and Diabetes in all age groups population. Furthermore, the growing geriatric population is another key factor which drives the Autologous Stem Cell and Non Stem Based therapies Market.

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Scope Of Market Reports

Autologous Stem Cell transplantation is a process in which cells from which all blood cells develop are removed, preserved and later given to the same person after severe treatment. In autologous stem cell transplantation, the patient itself acts as stem cell donor. These cells are collected in advance while they are in remission and returned to the patient at a later stage i.e., after two months. They are used to replace stem cells which have been impaired by high doses of chemotherapy.It is important to realize that the processes required in a stem cell transplant are lengthy and complicated. A transplant involves a lot of preparation and a lot of care after procedure. Many people have a single autologous stem cell transplant while others mainly having myeloma or tumors; have two or more continuous transplants.

The initial step in an autologous stem cell transplant is gathering the stem cells. Physicians usually collect stem cells from the bloodstream (peripheral blood stem cells) in advance. A mobilization treatment is used. When the stem cells are in the bloodstream, then collection process starts.The blood is separated using an Apheresis machine. This procedure requires a few hours, and is repeated until the appropriate amount of stem cells is collected. Once the stem cells are harvested, they are frozen in our Stem Cell Processing and Cryopreservation Laboratory until its time to transplant.

Autologous Stem Cell and Non Stem Based therapies Market is segmented on the basis of Application, product, End user and Geography. Based upon ApplicationAutologous Stem Cell and Non Stem Based therapies Market is classified as Neurodegenerative Disorders,Autoimmune Diseases, cancer &Tumors, Cardiovascular Diseases and Others. Based on the ProductAutologous Stem Cell and Non Stem Based therapies Market is classified into Blood Pressure Monitoring Devices, Pulmonary Pressure Monitoring Devices and Intracranial Pressure Monitoring Devices. On the basis of End users Autologous Stem Cell and Non Stem Based therapies Market is classified into Hospitals, Ambulatory Surgical Centers and Others.

The regions covered in Autologous Stem Cell and Non Stem Based therapies Market report are North America, Europe, Asia-Pacific and Rest of the World. On the basis of country level, Global Melanoma Drug Market sub divided in to U.S., Mexico, Canada, U.K., France, Germany, Italy, China, Japan, India, South East Asia, GCC, Africa, etc.

Rising prevalence of cancer and diabetes among people across all age groups, growing geriatric population, increasing demand for autologous stem cell and non-stem cell based therapies is another factor, which is likely to create a heightened demand. Moreover, Favorable reimbursement policies across several nations are also boosting market. Risks and complications associated with the Autologous Stem Cell and Non Stem Based therapy such as diarrhea, hair loss, nausea, severe infections, vomiting, heart complications, and infertility and thehigh cost of autologous cellular therapies ranging from $500,000 to $1,000,000 restraint the market. Innovation of some newtherapies with improved efficacy, fewer side effects are expected to offer good opportunity for growth of Autologous Stem Cell and Non Stem Based therapies Market in the future.

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North America is probable to attain the largest share of the Autologous Stem Cell and Non Stem Based therapies Market in terms of revenue and expected to hold the position followed by Europe region. This is due to less risk related with the treatment. Also, the demand for these treatments is high due to their ability to cure a significant number of infectious diseases. Autologous stem cell and non-stem cell based therapies do not require an outside donor hence the treatment is less infectious and cheap. However, Asia Pacific is expected to show the high growth in the forecast period. The demand in this region will be led by countries such as China, India, Malaysia, and Vietnam. The demand is likely to grow as autologous stem cell and non-stem cell based therapies aid in the efficient management of cardiovascular diseases as well. Rising healthcare facilities as well as increasing tax and reimbursement procedures is also estimated to help in the growth of the autologous stem cell and non-stem cell based therapies market in the Asia Pacific.

Furthermore, increase in awareness of disease and government initiatives for improving health care facilities are expected to boost the regional market to a certain extent.

By Application Analysis Neurodegenerative Disorders, Autoimmune Diseases, Cancer & Tumors, Cardiovascular Diseases, Others

By Product Analysis Blood Pressure Monitoring Devices, Pulmonary Pressure Monitoring Devices, Intracranial Pressure Monitoring Devices, Others

By End User Analysis Hospitals, Ambulatory Surgical centers, Others

North America, US, Mexico, Chily, Canada, Europe, UK, France, Germany, Italy, Asia Pacific, China, South Korea, Japan, India, Southeast Asia, Latin America, Brazil, The Middle East and Africa, GCC, Africa, Rest of Middle East and Africa

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Autologous Stem Cell and Non Stem Based therapies Market Share, Size 2021 Global Industry Future Trends, Growth, Strategies,, Segmentation, In-depth...

Lauren Sanostill wonders,if things were different, whether her father's life couldhave been saved.

"You always wonder if there was someone in the registry who was a bettermatch would have resulted in better outcomes and less transplant complications."

Mark Sanowas a 52-year-old Toronto father of three. He worked in the financial industry as a marketing manager and in his spare time was an avid sportsman who loved tennis, hockey and especially skiing.

In November of 2019 he was diagnosed with a rare form of leukemia. The only thing that couldsave his life, doctors told his family,was a stem cell transplant;a critical treatment for blood cancers and dozens of other diseases.

According to Canadian Blood Services (CBS), stem cells are the body's basic building blocks the raw material from which all cells are made. In blood, stem cells can become red, white blood cells or even blood platelets.

"Without stem cells, the body cannot make the blood cells needed for the immune system to function," CBS says, which runs the national blood bank.

It says a patient must find a match with a donor, and that is usually a person who shares the same ethnic background.

CBS says right now, donors to Canada's blood stem cell registry are more than two-thirds Caucasian, with the other third fracturedin uneven splintersacross race and ethnicity.

It means an Asian patient like Sano, according to the Canadian Blood Services stem cell registry, would have anywhere from seven to less than one per cent chanceof finding a match, depending on hisparticular genetic background.

So when the Sano family sought a match, they found a lack of minority donors who were aclose enough. Sano's daughter Lauren was the closest they could find and even then, she was far from ideal.

"I ended up being a half-match for him and was his donor.It was the most fulfilling and grounding experience."

As fulfilling as it was, it wasn't enough.Sano died at Princess Margaret Hospital in October 2020, 18 months after he was first diagnosed.

Lauren still wonders, whether her dad's life could have been saved, had they found the right donor from a more racially diverse pool of donors.

"I feel very lucky I was able to give him the gift of life.I was at least grateful that I was able to do this for my dad."

The dearth of diversity in Canada's stem cell registry is a problem Canadian Blood Services is familiar with, according toHeidi Elmoazzen, the agency's director of stem cells. Shehas been actively working on increasing the pool of minority donors to give minority patientsa better shot at getting better.

"We find that people tend to find matches within the same ethnic or racial background as them, which is why we're trying to build a registry that reflects the unique diversity we have here in Canada."

Some groups are more diverse than others when it comes to the make up of their stem cells, according to Elmoazzen. For example, she saysBlack people tend to be the most diverse.

A Black person whose ancestors are from the Caribbean might not have the same markers as someone from say, eastern Africa, which makes finding a match challenging.

Adding to the complication is that to harvest stem cells, you literally need young blood.Only young people, between the ages of 17 and 35 can apply.

The ongoing COVID-19 pandemic has also disrupted recruitment efforts, Elmoazzen says.Canadian Blood Services finds 60 to 70 per cent of its potential stem cell donors during its community clinics and with everyone staying home, the number of people visiting is down.

"It's had a heavy impact on our ability to recruit donors this year," she adds.

Still, virtual drives are underway. People interested in donating can still sign up through the Canadian Blood Services website.

There are also volunteers like Lauren Sano, who along with a number of Western University students will be pushing for donations in a virtual blood stem cell drive this month in honour of Black History Month and in April.

The hope is that by reaching out to diverse communities, Sanosays her goal is to help people make donating blood a habit. She says she hopes that willnot only will boost the blood supply, but the supply of blood products, such as stem cells and platelets as well.

See more here:
Canada's blood supply has a diversity problem and people are dying because of it - CBC.ca

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of an expanded label for KEYTRUDA, Mercks anti-PD-1 therapy. The opinion is recommending KEYTRUDA as monotherapy for the treatment of adult and pediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option.

This recommendation is based on results from the pivotal Phase 3 KEYNOTE-204 trial, in which KEYTRUDA monotherapy demonstrated a significant improvement in progression-free survival (PFS) compared with brentuximab vedotin (BV), a commonly used treatment. KEYTRUDA reduced the risk of disease progression or death by 35% (HR=0.65 [95% CI, 0.48-0.88]; p=0.00271) and showed a median PFS of 13.2 months versus 8.3 months for patients treated with BV. The recommendation is also based on supportive data from an updated analysis of the KEYNOTE-087 trial, which supported the European Commissions (EC) approval of KEYTRUDA for the treatment of adult patients with relapsed or refractory cHL who have failed ASCT and BV or who are transplant ineligible and have failed BV. The CHMPs recommendation will now be reviewed by the EC for marketing authorization in the European Union (EU), and a final decision is expected in the first quarter of 2021. If approved, this will be the first pediatric indication for KEYTRUDA in the EU.

This positive opinion reinforces the importance of KEYTRUDA for certain adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma in the European Union, said Dr. Vicki Goodman, vice president, clinical research, Merck Research Laboratories. We look forward to the decision by the European Commission and will continue to expand our clinical development program in blood cancers with KEYTRUDA and our recently acquired investigational therapies to help address the unmet needs of patients.

Merck is studying KEYTRUDA across hematologic malignancies through a broad clinical program, including multiple registrational trials in cHL and primary mediastinal large B-cell lymphoma and more than 60 investigator-initiated studies across 15 tumors. In addition to KEYTRUDA, Merck is evaluating two clinical-stage assets for the treatment of patients with hematologic malignancies: MK-1026 (formerly ARQ 531), a Brutons tyrosine kinase inhibitor, and VLS-101, an antibody-drug conjugate targeting ROR1.

About KEYNOTE-204

KEYNOTE-204 (ClinicalTrials.gov, NCT02684292) is a randomized, open-label, Phase 3 trial evaluating KEYTRUDA monotherapy compared with BV for the treatment of patients with relapsed or refractory cHL. The primary endpoints are PFS and overall survival (OS), and the secondary endpoints include objective response rate (ORR), complete remission rate (CRR) and safety. The study enrolled 304 patients, aged 18 years and older, who were randomized to receive either:

About Hodgkin Lymphoma

Hodgkin lymphoma is a type of lymphoma that develops in the white blood cells called lymphocytes, which are part of the immune system. Hodgkin lymphoma can start almost anywhere most often in lymph nodes in the upper part of the body, with the most common sites being in the chest, neck or under the arms. Worldwide, there were approximately 83,000 new cases of Hodgkin lymphoma diagnosed, and more than 23,000 people died from the disease in 2020. In the EU, there were nearly 20,000 new cases of Hodgkin lymphoma diagnosed, and nearly 4,000 people died from the disease in 2020. Classical Hodgkin lymphoma accounts for more than nine in 10 cases of Hodgkin lymphoma in developed countries.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,300 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS 10), as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% of these patients interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA with Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen, which was at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1). All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other antiPD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after antiPD-1/PD-L1 treatment. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between antiPD-1/PD-L1 treatment and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using antiPD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an antiPD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

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Merck Receives Positive EU CHMP Opinion for Expanded Approval of KEYTRUDA (pembrolizumab) in Certain Patients With Relapsed or Refractory Classical...

In KEYNOTE-598, the addition of ipilimumab to KEYTRUDA did not improve overall survival or progression-free survival, and patients who received the combination were more likely to experience serious side effects than those who received KEYTRUDA monotherapy, said Dr. Michael Boyer, chief clinical officer and conjoint chair of thoracic oncology, Chris OBrien Lifehouse, Camperdown, NSW, Australia. KEYTRUDA monotherapy remains a standard of care for the first-line treatment of certain patients with metastatic non-small cell lung cancer whose tumors express PD-L1.

As a leader in lung cancer, we are pursuing a broad clinical program to better understand the potential of KEYTRUDA-based combinations to improve survival outcomes for patients with this devastating disease, said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. KEYNOTE-598 is the first head-to-head study designed to answer the question of whether combining KEYTRUDA with ipilimumab provided additional clinical benefits beyond treatment with KEYTRUDA alone in certain patients with metastatic non-small cell lung cancer. The results are clear the combination did not add clinical benefit but did add toxicity.

These results were presented in the Presidential Symposium at the IASLC 2020 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer on Friday, Jan. 29 and published in the Journal of Clinical Oncology. As previously announced in Nov. 2020, the study was discontinued due to futility based on the recommendation of an independent Data Monitoring Committee (DMC), which determined the benefit/risk profile of KEYTRUDA in combination with ipilimumab did not support continuing the trial. The DMC also advised that patients in the study discontinue treatment with ipilimumab/placebo.

KEYNOTE-598 Study Design and Additional Data (Late-Breaking Abstract #PS01.09)

KEYNOTE-598 (ClinicalTrials.gov, NCT03302234) is a randomized, double-blind, Phase 3 trial designed to evaluate KEYTRUDA in combination with ipilimumab compared to KEYTRUDA monotherapy as first-line treatment for patients with metastatic NSCLC without EGFR or ALK genomic tumor aberrations and whose tumors express PD-L1 (TPS 50%). The dual primary endpoints are OS and PFS. Secondary endpoints include objective response rate (ORR), duration of response (DOR) and safety.

The study enrolled 568 patients who were randomized 1:1 to receive KEYTRUDA (200 mg intravenously [IV] on Day 1 of each three-week cycle for up to 35 cycles) in combination with ipilimumab (1 mg/kg IV on Day 1 of each six-week cycle for up to 18 cycles); or KEYTRUDA (200 mg IV on Day 1 of each three-week cycle for up to 35 cycles) as monotherapy. Non-binding futility criteria for the study were based on restricted mean survival time (RMST), an alternative outcome measure estimated as the area under the survival curve through a fixed timepoint. The pre-specified criteria were differences in RMST for KEYTRUDA in combination with ipilimumab and KEYTRUDA monotherapy of 0.2 at the maximum observation time and 0.1 at 24 months of follow-up.

As of data cut-off, the median study follow-up was 20.6 months. Findings showed the median OS was 21.4 months for patients randomized to KEYTRUDA in combination with ipilimumab (n=284) versus 21.9 months for those randomized to KEYTRUDA monotherapy (n=284) (HR=1.08 [95% CI, 0.85-1.37]; p=0.74). The differences in RMST for KEYTRUDA in combination with ipilimumab and KEYTRUDA monotherapy were -0.56 at the maximum observation time and -0.52 at 24 months, meeting the futility criteria for the trial and confirming the benefit/risk profile of the combination did not support continuing the study. Additionally, the median PFS was 8.2 months for patients randomized to KEYTRUDA in combination with ipilimumab versus 8.4 months for those randomized to KEYTRUDA monotherapy (HR=1.06 [95% CI, 0.86-1.30]; p=0.72). In both arms of the study, ORR was 45.4%; the median DOR was 16.1 months for patients randomized to KEYTRUDA in combination with ipilimumab versus 17.3 months for those randomized to KEYTRUDA monotherapy.

No new safety signals for KEYTRUDA monotherapy were observed. Treatment-related adverse events (TRAEs) occurred in 76.2% of patients treated with KEYTRUDA in combination with ipilimumab versus 68.3% of patients treated with KEYTRUDA monotherapy. Of these TRAEs, 35.1% vs. 19.6% were Grade 3-5, 27.7% vs. 13.9% were serious, 6.0% vs. 3.2% led to discontinuation of ipilimumab or placebo, 19.1% vs. 7.5% led to discontinuation of both drugs and 2.5% vs. 0.0% (no patients) led to death. Additionally, immune-mediated adverse events (AEs) and infusion reactions occurred in 44.7% of patients treated with KEYTRUDA in combination with ipilimumab versus 32.4% of patients treated with KEYTRUDA monotherapy. Of these immune-mediated AEs, 20.2% vs. 7.8% were Grade 3-5, 19.1% vs. 7.1% were serious, 1.8% vs. 1.1% led to discontinuation of ipilimumab or placebo, 12.1% vs. 4.3% led to discontinuation of both drugs and 2.1% vs. 0.0% (no patients) led to death.

About Lung Cancer

Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon and breast cancers combined. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of all cases. Small cell lung cancer (SCLC) accounts for about 10% to 15% of all lung cancers. Before 2014, the five-year survival rate for patients diagnosed in the U.S. with NSCLC and SCLC was estimated to be 5% and 6%, respectively.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,300 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS 10), as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test.

This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA with Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1). All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other antiPD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after antiPD-1/PD-L1 treatments. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between antiPD-1/PD-L1 treatments and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using antiPD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an antiPD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

See more here:
Merck Presents Results From Head-to-Head Phase 3 KEYNOTE-598 Trial Evaluating KEYTRUDA (pembrolizumab) in Combination With Ipilimumab Versus KEYTRUDA...

The story of Belfast woman Eimear Gooderham (nee Smyth), who passed away after a brave battle with cancer and sparked awareness of the stem cell register in Northern Ireland, will be told in a UTV programme this week.

imear was diagnosed with Hodgkins Lymphoma, a type of blood cancer, in 2016 aged 22 and underwent a dozen rounds of chemotherapy.

She manage to beat the cancer in the spring of 2017 and was given the all-clear by doctors, only for the disease to return again a few weeks later.

The disease went into remission following an autologous stem cell transplant, which involved using her own cells and high-dose chemotherapy.

In 2018, however, the Hodgkins Lymphoma returned once again and doctors said Eimear required another stem cell transplant, but from an anonymous donor.

This prompted her father Sean to launch a campaign, alongside UTV, to get people to sign the stem cell register and eventually a match was found.

Eimear had surgery, but sadly she passed away in hospital of organ failure on June 27, 2019, after suffering complications.

She had been due to marry her fianc Phillip Gooderham in October 2019, however with her condition worsening the wedding was organised to take place in hospital before she passed away.

UTV presenter Sarah Clarke followed Eimears story from the summer of 2018 and now that story will be told in a special programme, Eimears Wish, airing this Thursday at 10.45pm.

The programme will feature extracts from her video diary and dad Sean and sister Seainin, share memories of Eimear and talk about the positive ways they have been dealing with their grief since she passed away.

Sean Smyth said he hopes the programme will highlight the need for more people in Northern Ireland to join the stem cell donor register, especially men aged between 16 and 30.

There is also a lack of age-appropriate care for teenagers and young adults with life threatening illnesses such as blood cancer, he said.

The current facilities and the environment in which our teenagers and young adults receive their treatment and care is very poor. There also needs to be better facilities for the childrens carers.

Sarah Clarke added: It was Eimears dying wish to raise awareness of stem cell donation and to help further research into the treatment to help others. And although this programme is an entirely different one from the one we set out to make, I hope that it will in some way help to do that.

Belfast Telegraph

See the original post:
Family of Belfast woman Eimear Gooderham (25) share memories and dealing with grief in special UTV programme - Belfast Telegraph

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On January 26, 2021, Governor Gavin Newsom announced that California would alter its previous plan to start offering vaccines to high risk adults under 65 in the next vaccination phase. Instead, future eligibility levels in the state will be determined solely by age.

The United States Centers for Disease Controls current non-binding recommendation is to offer vaccines to disabled and chronically ill people aged 1664 years with underlying medical conditions which increase the risk of serious, life-threatening complications from COVID-19 in Phase 1c. In many states that would mean eligibility in a month or two, once the current first phases are completed. That was the plan for California, too, until this past week.

This move in California deeply disappointed the disabled community, and intensified growing concern among disabled and chronically ill people nationwide.

In a January 28 press conference, Andy Imparato, Executive Director of Disability Rights California, explained that based on current rates of vaccine production, going strictly by age will mean disabled and chronically ill people wont have access until June.

Another speaker at the virtual press conference, San Francisco disabled activist Alice Wong, has been both profoundly affected by the Covid-19 pandemic, and active in drawing attention to the unique risks and hardships the virus poses to people with disabilities and chronic illnesses. Californias change in vaccination priorities spurred her to further action:

"When I found out that Governor Newsom was eliminating prioritization for groups under Phase 1C in the state's vaccination plan I felt a surge of rage and fear at the injustice of it all. In response, I tweeted with the hashtag #HighRiskCA as a way for people from multiple communities disproportionately impacted by the pandemic to share their stories.

This is a localized variation on a hashtag thats been active since the pandemic started in March 2020, #HighRiskCovid19. Another important hashtag that has since the beginning expressed the feelings of high risk populations is #NoBodyIsDisposable.

Other disabled people also spoke out at the January 28 press conference.

Elena Escalera, Ph.D. of St. Mary's College and the #NoBodyIsDisposable Coalition said that the prospect of being included in the next phase of vaccinations is encouraging to people with disabilities and chronic illnesses. But when those priorities were changed in California to leave out people with disabilities under 65, ... there went the glimmer of hope of survival.

Anesthesiologist and bioethicist Dr. Alyssa Burgart highlighted the deep disability bias at the core of these decisions.

The bias against people with disabilities is pervasive. It is pervasive in health care because many of these folks are largely invisible. As you can see, many of these speakers have been confined to their homes because of the pandemic, and how much this has truly limited their ability to be engaged.

And Claudia Center, Legal Director of the Disability Rights Education and Defense Fund, noted the multiple layers of disability and chronic illness discrimination that disabled and chronically ill people have faced throughout the pandemic, and which also intersect with racial and other biases. These issues have included not just the latest setbacks in vaccine prioritization, but also denial of Covid-19 treatment through crisis standards of care, disabled people not being allowed to bring essential support staff with them to the hospital, and lack of data collection on how the pandemic affects disabled people.

It seems like California is making this change in priorities so it can avoid complicated and subtle decision-making, and instead go by more easily confirmed age. If so, it will achieve this simplicity by throwing some of its highest risk populations under the proverbial bus. Whatever the reasons for this change, and whether or how long its current priority system stands, it is adding to an already tense undercurrent of feeling among people with disabilities all over the country. There is a growing fear and conviction that disabled and chronically ill people, and our very specific kinds of risk from COVID-19, are once again being misunderstood and overlooked.

Obviously, everyone who isnt a vaccine or Covid skeptic is anxious to get vaccinated for the virus. And we all face the same fundamental barriers to vaccination, such as lack of sufficient supply and clumsy distribution systems. Its also important to recognize that putting any group higher on a priority list by itself doesnt do much. You can be at the top of the list, but if you cant figure out how to get a shot, or if your local provider runs out of doses, you are out of luck.

However, disabled and chronically ill people generally have more reason than most to be anxious and impatient. Some specific disabilities and conditions dont put people at that much more of a risk from Covid-19 infection, serious illness, or death, but a great many do. This is not mere speculation or paranoia. It is a documented medical fact recognized by most medical and epidemiological authorities.

Plus, being disabled exposes us to other, less direct hardships from the pandemic. For one thing, disabled people are more likely to be institutionalized in congregate care like nursing homes, assisted living, and group homes making it impossible for us to isolate ourselves. Many others of us require home care, which is less risky than nursing homes, but still exposes us to vectors of infection that we cant really do much on our own to avoid.

In a Los Angeles Times Op-Ed, Tim Jin writes:

Many people with disabilities are dealing with comorbidities of health that make us more vulnerable if we get the virus, while routine contact with multiple caregivers and other people who support us increases our risk of being exposed to COVID-19 As a person with cerebral palsy who lives on my own with support, I am more at risk because I rely on my staff to help me. I am exposed to multiple support people who come and go each day.

And Its not just people with conditions conventionally seen as disabilities who face higher risk from Covid-19. In an article for CNN, organ transplant recipient Kendall Ciesemier underscores the risk to people with chronic illnesses and other specific medical conditions:

The ones with cancer, with HIV, who have recovered from a bone marrow, stem cell, or solid organ transplant are increasingly becoming deprioritized across the country, sent to the back of the vaccine line.

She adds that these more recent setbacks only add to the sense of hopeless invisibility disabled, chronically ill, and other marginalized people have experienced throughout the pandemic:

To me and many like me, living in this pandemic has provided a daily reminder that our needs are unseen to those around us, that our lives hold little value to those who refuse to wear masks, who gather in groups or fly to a vacation destination. This is especially true for immunocompromised Black and brown people, who are among the most marginalized.

As disabled and chronically ill people we arent saying we have to be the very highest priority. We also recognize that other groups, particularly the elderly, have also at various points during the pandemic been ill-served, forgotten, or written off as acceptable losses. Most of us agree that prioritizing elderly people and healthcare workers makes sense. But we are dismayed to see disabled people who dont fit these categories seemingly forgotten.

Prioritizing everyone over 65 or 75 certainly puts some disabled people at the front of the line. But while many elderly people are also disabled, most disabled people are not elderly. According to the U.S. Census, about 34% of Americans over 65 have some kind of disability, a substantially higher disability rate than for the overall population. But only about 27% of Americans with disabilities are over 65. Disability and age overlap, but only partly.

Likewise, prioritizing health care and congregate care employees and residents is important to the disabled community, but only addresses some of us, not the vast majority who dont live in these facilities. Everyone knows about the tragedy of infection and death in nursing homes. Fewer people realize the same risk to developmentally disabled people in large institutions and smaller group homes. Meanwhile, people with disabilities who live on their own, or at home with home care, are virtually forgotten.

As a result, while we are nominally recognized to be high risk, most states vaccine priorities fail to recognize people with disabilities and chronic health conditions as a priority. Despite CDC recommendations, only 6 states currently offer vaccines to high risk adults who arent either elderly or health care / long term care workers. Many of us face the real possibility of our high-risk conditions not being recognized at all, resulting in more unnecessary illness, death, and long-term suffering.

Given the present scarcity of vaccine doses though, what is the fairer answer? This question is often presented as a false choice between deciding when to vaccinate disabled people based on science, and giving priority to the disability community for social or political reasons. In fact, it should be a combination of the two.

Scientists may know better which specific chronic illnesses and disabilities are and arent higher risk for Covid-19. But they arent always good at knowing and remembering the other ways Covid-19 disproportionately affects and endangers disabled and chronically ill people. One reason why a lot of disabled people are getting not just anxious but angry is that so many of us know from experience that without our own deliberate advocacy, its entirely possible for disabled and chronically ill people to be simply overlooked.

Deciding in a more targeted way who should have earlier access to Covid-19 vaccines is hard. Nobody is saying its not. But simply going by age, or focusing on a few specific environments and professions, isnt the answer. Its not logical, scientific, or humane.

On the other hand, the new Biden Administration appears to be a little bit ahead of the game in recognizing disabled and chronically ill peoples higher risk, and making them a higher priority. Its initial Covid-19 proposals include:

Implementation is always difficult, but a few more basic recommendations arent hard to think of. For example:

Among the many fears generated by the Covid-19 pandemic, one affecting the disabled community from the start is that our fellow Americans and portions of our government just dont care as much if we die. This idea has its roots in over a hundred years of on and off enthusiasm for eugenics the idea that society is better off without disabled people, and that disabled people themselves are, in a sense, better off dead.

A more specific fear and a profound sense of insult took hold in the early days of the pandemic when the fact that elderly and disabled people were at much higher risk of death was reported as a way to reassure other Americans that at least they werent in danger. This also turned out to be untrue, but even if it had been, it was not a proud moment in the history of American bravery or solidarity. Things only looked worse when states and localities proposed rationing policies that would deny care to people with certain kinds of disabilities who got Covid-19 explicitly and in policy writing them off.

Now its already looking like the vaccine rollout might sacrifice or simply overlook disabled people. Its probably still an exaggeration to say, as many disabled people are saying now, on social media and elsewhere, They want us dead. But the slightly less dramatic assertion that They dont care about us honestly doesnt seem far fetched these days. And even if we have our fellow Americans and governments intentions all wrong, their actions have not been promising.

Theres still time for a turnaround, but that time is running out fast.

See the article here:
Disabled People Are Waiting, Anxiously, For Lifesaving Covid-19 Vaccinations - Forbes