StemCell Therapy

For Immediate Release: December 15, 2021

Today, the U.S. Food and Drug Administration approved Orencia (abatacept) for the prophylaxis (prevention) of acute graft versus host disease (aGVHD), a condition that occurs when donor bone marrow or stem cells attack the graft recipient, in combination with certain immunosuppressants. Orencia may be used in adults and pediatric patients two years of age or older undergoing hematopoietic stem cell transplantation (commonly known as bone marrow transplantation or stem cell transplantation) from an unrelated donor.

This is the first FDA drug approval for aGVHD prevention and incorporates real world evidence (RWE) as one component of the determination of clinical effectiveness. RWE is clinical evidence regarding the usage and potential benefits, or risks, of a medical product derived from analysis of real world data i.e., data relating to patient health status and/or the delivery of health care routinely collected data from a variety of sources, including registry data. There are significant ongoing efforts at the FDA to incorporate use of high-quality RWE to support regulatory decision-making.

Acute graft versus host disease can affect different parts of the body and become a serious post-transplant complication, said Richard Pazdur, M.D., director of the FDAs Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDAs Center for Drug Evaluation and Research. By potentially preventing the disease, more patients may successfully undergo bone marrow or stem cell transplantation with fewer complications.

Acute GVHD is a potentially fatal complication that can occur after stem cell transplantation when the donors immune cells (the graft) view the recipients body (the host) as foreign, and the donated cells attack the body. The chances of developing aGVHD increase when the donor and recipient are not related or are not a perfect match.

The safety and efficacy of Orencia in combination with immunosuppressant therapy in patients age six years and older who underwent stem cell transplantation from a matched or mismatched unrelated donor were evaluated in two separate studies.

One study, GVHD-1, was a double-blind, placebo-controlled trial of 186 patients who underwent stem cell transplantation from a matched unrelated donor and randomly received Orencia or a placebo in combination with the immunosuppressive drugs. The study measured severe (grade III-IV) aGVHD-free survival, overall survival and moderate-severe (grade II-IV) aGVHD-free survival six months after transplantation. While severe aGVHD-survival was not significantly improved in patients who received Orencia (87%) compared to patients who received a placebo (75%), patients who received Orencia saw a 97% overall survival rate compared to 84% for patients who received a placebo. For moderate-severe aGVHD-free survival, patients who received Orencia saw a 50% rate compared to 32% for patients who received a placebo.

Additional evidence of effectiveness was provided by GVHD-2, a registry-based clinical study conducted using real world data from the Center for International Blood and Marrow Transplant Research in patients who underwent stem cell transplantation from a mismatched unrelated donor. This study analyzed outcomes of 54 patients treated with Orencia for the prevention of aGVHD, in combination with standard immunosuppressive drugs, versus 162 patients treated with standard immunosuppressive drugs alone. The study measured overall survival six months after transplantation. Patients who received Orencia saw a 98% overall survival rate compared to 75% for patients who received standard immunosuppression alone.

The most common side effects of Orencia for prevention of aGVHD include anemia, hypertension, cytomegalovirus (CMV) reactivation/CMV infection, fever, pneumonia, nosebleed, decreased levels of specific white blood cells called CD4 lymphocytes, increased levels of magnesium in the blood and acute kidney injury. Patients who receive Orencia should be monitored for Epstein-Barr virus reactivation in accordance with institutional practices and receive preventative medication for Epstein-Barr virus infection before starting treatment and for six months post-transplantation. Patients should also be monitored for CMV infection/reactivation for six months post-transplant.

Orencia received Breakthrough, Orphan Drug and Priority Review designations for this indication. Development of this product was partially supported by the FDAs Orphan Products Grants Program, which provides grants for clinical studies on safety and efficacy of products for use in rare diseases or conditions.

Orencia was originally approved by the FDA in 2005 for the treatment of adult rheumatoid arthritis. Orencia is also approved for the treatment of polyarticular juvenile idiopathic arthritis and adult psoriatic arthritis.

The FDA granted approval of Orencia to Bristol Myers Squibb.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with Health Canada, Swissmedic and MOH (Israels Ministry of Health). The application reviews are ongoing at the other regulatory agencies.

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The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nations food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

12/15/2021

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FDA Approves First Drug to Prevent Graft Versus Host Disease | FDA - FDA.gov

Ongoing Phase 2 clinical trial for MAU868 in kidney transplant patients; potential first-in-class

MAU868 Phase 2 data for kidney transplant to readout mid-2022

BK Virus is a leading cause of transplant loss and transplant-associated morbidity

BRISBANE, Calif., Dec. 17, 2021 (GLOBE NEWSWIRE) -- Vera Therapeutics, Inc. (Nasdaq: VERA), a clinical-stage biotechnology company focused on developing treatments for immunological diseases that improve patients lives, announced today that it has acquired MAU868, a first-in-class monoclonal antibody to treat BK Virus (BKV) infections, and has entered into a credit facility with Oxford Finance LLC (Oxford) to provide borrowing capacity up to $50 million. MAU868, acquired from Amplyx Pharmaceuticals, Inc., a wholly owned subsidiary of Pfizer Inc., has the potential to neutralize infection by blocking BKV virions from binding to host cells.

BKV is a leading cause of kidney transplant loss and transplant-associated morbidity, and there are currently no available antiviral treatments in the U.S. We are excited to acquire MAU868 from Pfizer and carry it forward in development, said Vera founder and CEO Marshall Fordyce, MD. The acquisition of MAU868, a potentially transformative treatment for BKV, is consistent with our strategy to diversify our pipeline with new molecules that leverage our strengths and serve adjacent populations. We believe, based on currently available data, that MAU868 has the potential to significantly impact outcomes for kidney transplant patients and become the first effective therapy for BKV. We look forward to working with regulators to establish a new standard of care for kidney transplant patients.

MAU868 is currently undergoing a randomized, double-blind, placebo-controlled Phase 2 clinical trial to assess the safety, pharmacokinetics, and efficacy for the treatment of BKV in kidney transplant patients. MAU868 has been shown in an interim analysis of week 12 data from Cohort 1 and 2 of a Phase 2 study to be well tolerated and showed a greater proportion of subjects with decrease in BK plasma viral load versus placebo. Full Cohort 1 and 2 interim analysis results will be submitted for presentation at a conference in mid-2022.

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Up to 90 percent of healthy adults are infected with BKV, but it remains latent in kidney and bladder tissues. Reactivation occurs in the setting of immune suppression, and causes clinical disease in the transplant setting. BKV is a significant cause of complications in these immunocompromised patients, including in kidney transplant and hematopoietic stem cell transplant (HSCT) recipients. In kidney transplant recipients, BKV is a leading cause of allograft loss and poor outcomes, while in HSCT recipients, the virus significantly increases the risk of severe hemorrhagic cystitis, which causes bladder damage. There are currently no approved treatments for BKV in the U.S.

MAU868 Asset Acquisition In partial consideration for the asset acquisition, Vera made an upfront payment of $5.0 million. In addition to the upfront payment, Vera is also obligated to make certain milestone payments in an aggregate amount of up to $7.0 million based on certain regulatory milestones. Further, Vera is required to pay Amplyx low single-digit percentage royalties based on net sales on a country-by-country and product-by-product basis. The rights to MAU868 that Vera acquired from Amplyx are subject to a license agreement by and between Amplyx and Novartis International Pharmaceutical AG, pursuant to which Vera is obligated to make certain milestone payments in an aggregate amount of up to $69.0 million based on certain clinical development, regulatory and sales milestones. Further, the Company is required to pay Novartis mid-to-high single-digit percentage royalties based on net sales on a country-by-country and product-by-product basis.

Credit Facility Vera also announced today that they entered into a credit facility with Oxford Finance. Under the terms of the loan agreement, Oxford will provide Vera with borrowing capacity of up to $50 million. The initial $5 million funded at closing, and an additional $45 million will be available in minimum draws of $5 million, at Veras option through the end of 2022. The debt facility provides for at least 48-months of interest-only at close. There are no warrants or financial covenants associated with the credit facility. Armentum Partners served as the Companys financial advisor on the debt financing.

About VeraVera Therapeutics is a clinical-stage biotechnology company focused on developing treatments for serious immunological diseases. Veras mission is to advance treatments that target the source of immunologic diseases in order to change the standard of care for patients. Veras lead product candidate is atacicept, a fusion protein self-administered as a subcutaneous injection once weekly that blocks both B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), which stimulate B cells and plasma cells to produce autoantibodies contributing to certain autoimmune diseases, including IgA nephropathy (IgAN), also known as Bergers disease. Vera is also developing MAU868, a monoclonal antibody that neutralizes infection with BK Virus, a polyomavirus that can have devastating consequences in certain settings such as kidney transplant. For more information, please visit http://www.veratx.com.

Forward-looking Statements

Statements contained in this press release regarding matters that are not historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the potential efficacy of our product candidates, research and clinical development plans, the scope, progress, and results of developing our product candidates, strategy, regulatory matters, including the timing and likelihood of success of obtaining drug approvals, market opportunity and our ability to complete certain milestones, the timing of the expected closing of the debt financing, and the expected use of the net proceeds therefrom. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as plans, will, anticipates, goal, potential, and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Veras current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks related to the ability to realize the anticipated benefits of the acquisition, including the possibility that the expected benefits from the acquisition will not be realized or will not be realized within the expected time period, risks and uncertainties associated with Veras business in general, the impact of the COVID-19 pandemic, and the other risks described in Veras filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on managements assumptions and estimates as of such date. Vera undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

ContactsInvestor Contact:IR@veratx.com

Media Contact:Greig Communications, Inc.Kathy Vincentkathy@greigcommunications.com

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Vera Therapeutics Announces Acquisition of Monoclonal Antibody From Pfizer to Treat BK Virus in Transplant Patients - Yahoo Finance

Season for Caring: Rivera family, in cancer battle, looks for relief

Ashley Rivera has stage four breast cancer and a brain tumor. The family also has children with complex medical conditions.

Nicole Villalpando and Mikala Compton, Austin American-Statesman

In summer 2015, Joy Brooks threw a "Kick the Bucket" party with all her friends and family at her neighborhood park on Lake Buchanan.

"It was sad, but lovely," Brooks says. "I was so grateful to see all those smiling faces."

Her husband, Kevin, cooked 12 racks of ribs and a brisket. They decorated with buckets of daisies because she would soon be "pushing up daisies." They had a skeleton piata. People swam and waterskied in the lake.

By the time of the party, though, she was too sick to eat that barbecue. She was receiving hospice care and was starting to give away such things as jewelry and other special items.

Brooks at age 58 had been diagnosed with a rare cancer called pseudomyxoma peritonei, which started in her appendix beforespreading to an ovary and thenthroughout the peritoneum, the lining that covers the abdomen walland all its organs.

In June 2015, she was told her tumors had grown too large and too spread out to remove. She entered hospice care.

Then her daughters did an internet search for treatment options and found Dr. Rebecca Wiatrek, asurgical oncologistwith Texas Oncology Surgical Specialists in Austin, and learned of a possible treatment. Hyperthermic intraperitoneal chemotherapy washes the abdomen with a heated chemotherapy after as much of the cancer is scraped out as possible.

The need for this kind of treatment is growing, and Texas Oncology has hired a second specialist to dohyperthermic intraperitoneal chemotherapy.

"We are developing a program here where we can become a referral center for this,"Wiatrek says. "That doesn't happen in a city this size."

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The treatment is incredibly labor intensive.Wiatrek has to get rid of as much of the cancer as she can by first removing any large tumors and then scraping the lining. Sometimes parts of organs, such assections of the intestines or the stomach, have to be removed because of the amount of cancer and the way it's involving those organs.

"You can take out what the person can live without," Wiatrek says. "Only a few things in your abdomen you need leave in, like the liver and the small intestine, the rest of the stuff you can take out, but we try to save as much of the organs as possible," to make recovery easier.

This cancer is not like most tumors that thrive on a good blood supply and react well to chemotherapy delivered intravenously.

Instead, this cancer is more of a jellylike substance that doesn't rely on the blood supply to grow. That makes traditional chemotherapy ineffective.

"It's one of those odd cancers," Wiatrek says. "It's mostly mucus that doesn't have any cells in it. It's fat cells gone awry."

People have tried other therapies with this cancer, but "none has panned out,"Wiatrek says."We do get really good outcomes this way."

The surgery to remove the cancer and then wash the abdomen with hot chemotherapy typically takes about 10 hours, butWiatrek has done one that lasted as long as 21 hours.

"It's definitely a marathon,"Wiatrek says. Because it is so labor intensive,Wiatrek says she can do only one of these surgeries a week. With a second surgeon, Texas Oncology will be able to do two a week.

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This cancer is typically slow growing, and the symptoms can be easily missed. Brooks, who had been a meter reader for Pedernales Electric Cooperative, was very active, but she remembers having some intense cramps that felt like they were coming from her ovaries. They didn't happen all the time, maybe once every six weeks or every two months.

In October 2014, she went to the hospital forknee surgery. She was having complications, and doctors thought she had a blood clot, but ascan revealed amass on her appendix.

She was so focused on the knee recoverythat she didn't really focus in on what the doctor was trying to tell her. At a follow-up appointment, she was referred to MD Anderson Cancer Center in Houston, but wasn't put on the schedule there until February 2014.

In Houston, she was told her cancer was slow growingand to come back in June to have the tumor removed. By the time she arrived in June, her cancer had spread and the tumor around her ovary, which she didn't realize she had, had grown too large to remove.

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"That means I'm going to die," Brooks thought. They offered to do chemotherapy for the cancer around the ovary, but it wouldn't be effective for the cancer along theperitoneum. "Why do I fight the ovary tumor if the (cancer on the peritoneum) is going to kill me?" Brooks says.

Brooks had a son-in-law who hadcancer,wentthrough chemotherapy and didn't make it. She didn't want that. She wanted to focus on the time she had left.

"I didn't think there was anywhere to go," she says.

She and her family put together her farewell party.

"I wanted to see everybody that I knew and loved before I was too sick," she says, "I had gone downhillrapidly. I was having trouble breathing and couldn't eat a lot at one time."

The mass of cancer in her abdomen was pressing on everything.

She says during that time she was depressed and stayed in bed a lot. "Nobody wants to say goodbye to their family," she says."It was sad."

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Brooks had done onlinesearches for treatments. Sheoften found optionsin England, or in Boston, but she was too weak to travel by that point.

After her children found this treatment and Dr.Wiatrek just down the road in Austin, Wiatrek was able to see Brooks quickly and start talking to her abouthyperthermic intraperitoneal chemotherapy.

It's an intensive therapy that often takes a few office visits to really have the patient understand everything fully, Wiatrek says.

By this point, Brooks didn't have any other treatment options, but there was a concern about whether she was strong enough to undergo surgery.

"I knew if I could get the tumor out, and she could heal, she was going to make it," Wiatrek says. "It was going to be a long healing process."

Wiatrek could not operate on Brooks right away. "She was extremely malnourished," Wiatrek says."Whenyou don't have nutrition, you don't heal."

The tumors, especiallythe one on Brooks' ovary, were large and pushing on her intestines, making it difficult to eat.Brooks was weak from not being able to eat much for weeks.

Wiatrek toldBrooks that she had to get her strength up by drinking Ensure nutritional supplementfor three weeks.

"I could only drink 2 ounces at a time," Brooks says, but she did it.

Wiatrek says that if there was any way she could make this work, she was going to do it."I'm a glass-half-full kind of person," Wiatrek says,but "it has to be the right candidate."

Wiatrek knew that Brooks was a fighter. "Even when she was really sick, she had a lot of determination," Wiatrek says. For example, Brooks walked into her appointments with Wiatrek even when she shouldn't have physically been able to do it. "There's a lot to mental toughness," Wiatrek says.

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Brooks says she wasn't afraid of the actual surgery. "I just left it in God's hands," she says. She tried to think of it as getting some rest.

Brooks surgery was nine hours. "The (cancer) cells were pretty much everywhere," Wiatrek says.

While Wiatrekscrapped as much of the cells that she could and felt like she had gotten it all, "there's always a chance some of those cells could be left behind," Wiatrek says, which is why the heated chemotherapy treatment inside the abdomen is so key.

Patients get repeated scans, first every couple of months, then six months out, and then every year to see if any cancer has returned. Sometimes they have to repeat the surgery and chemotherapy treatment.

With Brooks, Wiatrek didn't have to remove anything that would be essential toher digestive system.

The healing was slow. Brooks was in the hospital 45 days after the surgery.She was kept heavily sedated and doesn't remember much of the first few weeks. At one point, her intestines were popping through the surgical wound that was having trouble closing. Wiatrek took her back into surgery to secure her intestines. She was given a stem cell treatment to aid in the healing.

She also developed fluid in her lungs that had to be drained.

Brooks, though, was able to continue the healing at home, including wound care.

"It was a very lengthy ordeal," Brooks says, but it wasn't without moments of joy. On her birthday in October that year, her second granddaughter was born. It wasn't a birthday she expected to see, and "I didn't think I was going to live long enough to see that baby born," Brooks says. She's since had a third grandchild born.

"I'm just testimony to the power of divine intervention and tenacious children and a doctor that would not give up," Brooks says.

With every scan that she has to check for cancer, there has been good news. "Every year we get farther out, the more we feel like it won't ever come back for her," Wiatrek says."Joy's outcome has been great."

Brooks has since donated back the hospice bag she received.

"We're blessed," Brooks says. "We're just grateful. When you go through something like we've been through, you're grateful for all the people in your life and you're grateful for your faith.

Link:
After throwing goodbye party, woman with cancer finds hope close to home in Austin - Austin American-Statesman

Published on December 21, 2021

First of a kind training in a village in India to medically grow most common transplanted organs

Chennai : Dr. K.M. CHERIAN HEART FOUNDATION & EDUCATIONAL SOCIETY organized a four-day CME program with workshop on Cell Culture and Regenerative Medicine at Frontier Mediville, Thiruvallur District, Chennai from 14th to 17th December 2021. With an initiative to provide hands-on training to candidates in cities and villages about methodologies to grow most transplanted solid human organs such Kidney, Liver, Heart, Lungs and Pancreas. This training is first ever in India at Frontier Mediville (Dr. K.M. Cherian Heart Foundation & Educational Society) to provide affordable healthcare opportunities to patients. This treatment has very less complications and is easily adoptable across India.

Four day elaborate scientific deliberations took place and the programme was inaugurated by Prof. K. VijayRaghavan, Principal Scientific Adviser to Honble Prime Minister of India. The programme was attended by prominent personalities like Padmabhushan Dr. T. Ramaswamy, Former Secretary, Department of Science and Technology and Dr. Sanjeev Kumar, Dy. Drugs Controller representing the Drugs Controller General of India.

The main objective of the CME program and workshop was to discuss on the approach to research in newer medical technologies to advance and discover clinical solutions. The growing demands for much needed transplant organs has gross mismatch with regard to supply. The regulatory restrictions, logistics and the need for anti-rejection treatment comes in the way of patients getting transplanted. Growing organ from own cells will not have rejection. This workshop being affordable healthcare to India. Dr. K.M. Cherian Heart Foundation & Educational Society is the first to bring in the concept of Bio-Hospital, inspired by the amalgamation of traditional and modern medicine, thus a holistic approach to overall treatment.

Dr. K. M. Cherian welcomed the Guest of Honor Padmabhushan Dr. T. Ramaswamy, Former Secretary, Department of Science and Technology and other delegates attending the event. Dr. Sanjeev Kumar, Dy. Drugs Controller representing the Drugs Controller General of India, also stressed on the need of traditional medicine in his session on AYUSH, the holistic approach to healthcare,

The Cardiac Transplant pioneer Dr. K M Cherian, Chairman, Dr. K.M. Cherian Heart Foundation & Educational Society said With cardiovascular disease the leading cause of death, cell culture and cardiac regeneration has become a topic of interest worldwide. Frontier Lifeline Hospital is constantly adopting new technologies to offer best treatment to the patients.

Speaking at the event, Prof. K. VijayRaghavan highlighted the importance of basic research in this country and the translation of Regenerative medicine in to clinical practice even though ideal but cannot be materialized due to many reasons. The most important aspect is implementation of affordable health care.

Dr. Robert Klempfner, Director Innovation Center, Sheba International, Israel and Dr. Kathy Jenkins, Prof. of Pediatric Cardiology, Harvard University, Boston were some of the key speakers who took part in this recent Innovative Health Care.

Dr. Ramaswamy stressed on the need for the Government support and talked about the projects which are available under DBT, TDB, CSIR schemes.

Dr. Sanjeev Kumar emphasized on the need for newer drug discoveries and India has not been able to produce even one new novel drug molecule.

Dr. Ramchand, CEO of MagGenome talked about the successful development of a low cost RT-PCR kit in Chennai which has been supplied Tamil Nadu State at a very short notice.

Mr. Sivaprasad, CEO of PolySkin Life Sciences, a start up in Kerala, demonstrated the technical importance of production of scaffold, cell seeding and 3D cell culture depending upon the organ you want to grow.

Dr. Balasundari, Former Research Associate in Frontier Lifeline from US talked about the 3D cell culture including technologies developed even to convert Spinach leaves in to beating heart.

In the light of the event, Ms. Thushara, CEO of SOS Holdings signed an MOU with Dr. K.M. Cherian during the advance course on scientific approach to research in newer medical technologies, for training the candidates with support for placement schemes.

Dr. K.M. Cherian Heart Foundation & Educational Society also signed a MoU with Kaunas University, Lithuania. It has been implemented as per Vice Chancellor Prof. Rimantas Benetis. The MoU is designed to help candidates from India to obtain world class training and to be a preferred choice for placement in any European Union countries.

The four day workshop was participated by Scientists who are involved in research in the field of stem cells, tissue engineering, growing organoids leading to solid organs and 4D Printing. Along with scientific session there was hands-on training in cell seeding, scaffold creation for the first time in the country. There was opportunity to dissect heart and lungs during the anatomy session. There was teaching modules for young scientists, the pathways for medical research methodologies. The CME and workshop has shown that these sophisticated modern technologies can be even made practical in a village which will be affordable for the patients.

The Korona Guard candy has been proved highly effective (98.4%) as per IRSHA (Interactive Research School for Health Affairs) Pune, against all covid-19 variants in Invitro trial of the medicine. One clinical study and placebo study with 100 patients has been conducted already for Korona guard candy by Frontier Mediville in association with Tamil Nadu Health Ministry at Gummidipoondi. Its efficacy has been proven to be 5 times more potent in reducing viral load. Its a low cost and non-complicated medicine for adults and children alike. It is easily available in all Sundar Dezire outlets.

Link:
Dr. K.M. Cherian Heart Foundation & Educational Society Organized Cme Programme & Workshop On Cell Culture And Regenerative Medicine - APN...

2004 Saint Anselm alum Greg Grappone had his lifes ambitions and virtues memorialized in the form of a institute for humanities situated behind Alumni Hall.

At age 35, Grappone passed on May 1, 2015 in Seattle after complications from a graft-versus-host disease succeeding a stem cell transplant for a rare form of cancer. Grappone led his life as a father, a husband, and a son, and after graduating he found himself as the owner of his familys car dealership that stretches Route 3A in Bow, New Hampshire. The Grappone company was said to have been built upon a philanthropic reputation which parallelled the way in which Greg Grappone held himself. Grappone held a deep passion regarding cultural, social and political issues. He relished in his own personal pursuit for truth regarding these subjects, and it was because of this that he was seen as an inspiration to all. Grappone, as this type of intellect, spent much of his life grounded by lifes unanswerable questions.

Grappones consistent search to understand the world around him demonstrated a clear path in becoming a Great Books major for the Saint Anselm class of 2004. His adventures saturated in curiosity were accompanied by the stories the Great Books told; to which he viewed them as life companions rather than just educational implements Grappone luxuriated in the wisdom that these books provided and the questions and conversations that they provoked. One of Grappones professors, Father John, depicted the extent of Grappones intellectual curiosity by explaining how [Greg was] very interested in learning and eager to discuss the Great Books we read not only for their content but also for how they could help him be a better person. As a professor, it is always a pleasure to work with a student whose primary focus is learning, not grades. This pursuit of higher intellect was bolstered by Grappones person as a whole, as he was praised for, His great attitude and kindly, gentlemanly manner.

Grappones fascination for the humanities had fostered the foundation for a permanent home for the cultivation of intellect on the Saint Anselm campus. In an article to the Concord Monitor, Gregs parents, Robert and Beverly discussed how they were searching for a meaningful way to honor their sons memory, and it was at this time where Saint Anselm College was in search of enlivening their humanities department. The brevity of Grappones life ended with daily correspondence with his father and American filmmaker Ken Burns. The three would engage in conversation surrounding wisdom laid forth by Russian author and philosopher Leo Tolstoy. Because of the relationship that Grappone and Burns shared, Burns served as the honorary chair of the new humanities building campaign on campus. Grappones parents, in recognition of the importance in further the development of higher education stated, We believe that now more than ever we all need to do what we can to enlighten our minds, feed our souls and lift our spirits and those of others by heeding the instructions of Tolstoy: you have to embrace what the wisdom of humanity, your intellect and your heart tell you: that the meaning of life is to serve the force that sent you into the world. Then life becomes a joy.

Father John, in acknowledging the life lessons that Grappone exemplified as a student, stated that students could take away this lesson: Focus on learning, not on grades! Strive to be a better person today than you were yesterday. It is because based upon this mindset, that Grappone will forever be remembered at the Saint Anselm campus.

Donations can be made to the following causes that were identified as meaningful to the Grappone name, found in the Concord Monitor 2015:

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Namesake of new center a young man in love with the pursuit of knowledge - The Saint Anselm Crier

RICHMOND, Ind. The next Red Cross blood drive is focusing on the fight against sickle cell disease.

The local blood drive will participate in the national effort, according to Dana Mollenkopf, who has been with the local Red Cross nine years. The drive will be noon-5 p.m. Dec. 21 in the lower-level multipurpose room at Central United Methodist Church, 1425 E. Main St.

COVID-19 protocols will be followed during the blood drive, and blood samples will be tested for COVID antibodies, according to Mollenkopf. Blood samples from Black donors also will be tested for sickle cell traits, with results available to donors in one to two weeks.

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About 10% of Black people carry the sickle cell trait, according to the American Society of Hematology. Although sickle cell disease disproportionately impacts Black people, only 3% of blood donors nationwide are Black, Mollenkopf said, andBlack donors are encouraged to register for the Dec. 21 drive to help fulfill the need for blood.

Appointments may be made at redcrossblood.org with the CUMCRICH code.

As an organization dedicated to alleviating suffering, the Red Cross is committed to the health and well-being of all communities, and a diverse blood supply is critical to improving health outcomes for all patients especially those with sickle cell disease," said Gail McGovern, CEO and president of the Red Cross, in a news release. For someone facing a sickle cell crisis, a blood transfusion can make a lifesaving difference.

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Sickle cell is the most common genetic blood disease in the United States, according to the Red Cross. Patients often rely on regular blood transfusions to avoid complications such as organ and tissue damage, severe pain and strokes. The disease is only cured by stem cell or bone marrow transplants or emerging gene therapy, but such treatments are not widely available.

The blood used in those transfusions must be the most compatible match possible, which usually comes from someone of the same race or from a similar ethnicity. Donated blood will also be utilized for other emergency uses.

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Red Cross blood drive focuses on sickle cell disease fight - Palladium-Item

Success Story of Extracorporeal Shock Wave Therapy (ESWT)

Successful for over 40 years in urology for the disintegration of kidney stones, with high efficiency and hardly any side effects worth mentioning.

How does the shock wave work?

Without causing mechanical damage, shockwaves trigger a biological response in the treated tissue through their compressive, tensile and shear forces (mechanotransduction). Genes are activated in the cell nucleus starting to produce proteins (including growth factors) responsible for the healing process. This also causes increased ingrowth of newly formed blood vessels, which improves local metabolism. The additional modulation of the inflammation necessary for healing enables regeneration of pathological tissue.

Recent studies prove.

Shockwaves also trigger the production of messenger substances to the cell nucleus, which mobilize the body's own stem cells from the bone marrow, stimulating them to migrate to the treated tissue, settle there and develop into the required tissue (e.g. heart muscle cells). Instead of conventional stem cell transplantation shockwaves make it possible to initiate the body's own regeneration without risk of complications.

Therapy for a wide variety of tissues.

Since the underlying pathology can be treated with these methods, shockwave therapy is being used in more and more medical disciplines.

This creates a tool that opens up completely new possibilities in tissue regeneration without triggering significant side effects. Since conventional medicine has not been able to offer any significant therapeutic options to date, the present results of shockwave therapy are of particular importance and are therefore applied in the following areas. It can be assumed that shockwave therapy can be used in practically all medical specialties.

Spinal cord injury/cross-sectional lesion.

What was long considered unthinkable is now one of the major hopes for causal therapy: shockwave has also made great progress in the treatment of paraplegia. Since November 2020, the first patients have been included in an Austria-wide study. Due to the COVID pandemic, the initiation of the individual study centers has been somewhat delayed, but so far eight patients have already been enrolled in the study. In addition, the Unfallkrankenhaus Berlin, one of the most important centers for spinal cord injury in Germany, will participate in the study.

Dr. Wolfgang Schaden, adj. Prof., President of ISMST, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Deputy Medical Director of AUVA, Austria

Cardiac Surgery.

Regeneration of heart muscle after myocardial infarction has long remained a dream of modern medicine. Despite extensive efforts to develop stem cell and gene therapies, none of these methods could be brought into clinical routine. Cardiac shockwave therapy brings a scientific breakthrough: Cardiac function is improved, and impressive results show the increase of patients' quality of life. Shockwave therapy in cardiac surgery has a favorable side effect profile and is on the verge of bringing cardiac regeneration into daily clinical practice.

PD Dr. Johannes Holfeld, University Department of Cardiac Surgery, Innsbruck Medical University, Austria.

Sexual Medicine.

Low-energy shockwave therapy has been a fabulous addition to sexual medicine armamentarium for men and women with various forms of sexual dysfunction, e.g. erectile dysfunction, premature ejaculation, persistent genital arousal disorder PGAD/genito-pelvic dysesthesia GPD. Many patients (and their partners) describe these comfortable and quick shockwave treatments as life changing.

Prof. Dr. Irwin Goldstein, Alvarado Hospital, San Diego, CA, USA

Aesthetic-, hand-, burn- and reconstructive surgery.

Shockwave medicine can support these four pillars of surgery noninvasively. Two significant examples: In aesthetic surgery with significant improvement in cellulite with shockwave therapy after six to eight sessions, lasting for a period of about one year. In burns, shockwave therapy can accelerate epithelialization (healing) of superficial burn injuries clinically relevant by three days, with a significant reduction in infections and hospitalization.

Prof. Dr. Karsten Knobloch, SportPraxis Prof. Knobloch, Hanover, Secretary General of the German Shockwave Society DIGEST.

Sports Medicine.

After more than 30 years of experience, shock wave treatment is now a standard in sports medicine and rehabilitation facilities worldwide.

Leprosy.

Shockwaves used in a similar way as for diabetic foot ulcers have also led to the healing of wounds in leprosy patients and significantly improved the quality of life of these patients. This work, carried out in Agua de Dios, Colombia, by the Bosque University group in Bogot, is now being used in several medical centers around the world with very positive results.

Prof. Dr. Carlos Leal, Bosque University, Fenway Medical, Bogot, Colombia.

Wound healing.

Chronic wounds are challenging for patients concerned and practitioners and will have an increasing impact on health care systems. Treatment with shockwaves has a positive conditioning influence on the wounds and in a high proportion for healing, independent of otherwise aggravating factors (e.g. diabetes mellitus, immunosuppression, cortisone therapy, and other exacerbating factors).

With an average treatment frequency of one treatment every second week, in addition to the established wound therapy, healing was observed in more than 70% of the cases of ulcers and other wound healing disorders.The therapy is free of side effects and helps to reduce the burden of the health care system due to the enormous savings potential.

Rainer Mittermayr, MD, MBA, assoc. Prof., Treasurer of the ISMST and Conference Secretary, Senior Surgeon Orthopedic and Traumatology, AUVA (Austrian Workers Compensation Board, Vienna, Austria)

Originally posted here:
Shockwave therapy brings new healing opportunities for heart attack patients and hope for people with spinal cord injuries - KULR-TV

The U.S. Food and Drug Administration approved the start of a first clinical trial of CRISPR_SCD001, the first non-viral and CRISPR/Cas9-based gene editing therapy for sickle cell disease(SCD).

Both the therapy and the upcoming Phase 1/2 trial planned to start this summer are the result of a collaboration between the Innovative Genomics Institute (IGI) and the University of California (UC), Los Angeles (UCLA).

IGI, a joint research initiative between UC Berkeley and UC San Francisco (UCSF), was founded by Berkeleys Jennifer Doudna, PhD. Doudna,along with Emmanuelle Charpentier of France, was awarded the 2020 Nobel Prize in Chemistry for groundbreaking work on the CRISPR-Cas9 gene editing tool.

Similar to the editing system used by bacteria as a defense mechanism, CRISPR-Cas9 allows researchers to edit parts of the genome by adding, removing, or changing specific sections of DNA.

We are motivated to work towards a cure that can be accessible and affordable to patients worldwide, Doudna said in a press release.

The launch of this trial is an essential first step on that path, added Doudna, who first approached the team at UCSF Benioff Childrens Hospital Oakland with the idea of developing a CRISPR/Cas9-based cure for SCD in 2014.

CRISPR_SCD001 uses the power of the CRISPR-Cas9 gene editing system to replace the mutatedHBB gene in a patients hematopoietic stem cells with a healthy version. The HBB gene, whose mutation cause SCD, provides the instructions to produce the beta subunit of hemoglobin, a protein found in red blood cells that transports oxygen.

These stem cells, which can give rise to all types of blood cells, are collected from a patients bone marrow, genetically modified in the lab with the innovative tool, and then returned to the patient in the form of a stem cell transplant.

By restoring production of normal hemoglobin and preventing red blood cells from becoming damaged and acquiring a sickle shape, the therapy is expected to be a potential cure for SCD.

Mark Walters, MD, the trials principal investigator and a professor of pediatrics at UCSF, said the goal of this form of genome-editing therapy is to correct the mutation in enough stem cells so the resulting blood in circulation has corrected red blood cells.

Based on previous bone marrow transplants, we predict that correcting 20% of the genes should be sufficient to out-compete the native sickle cells and have a strong clinical benefit, added Walters, who is also director of the blood and marrow transplant program at Benioff Childrens Hospital Oakland.

Unlike other investigational gene editing approaches for sickle cell, CRISPR_SCD001 delivers the CRISPR-Cas9 machinery to cells without relying on a virus as a transport agent. Its method, called electroporation, uses electrical pulses to create temporary pores in cell membranes that allow for the gene-editing tool to enter.

As such, the upcoming Phase 1/2 trial (NCT04774536) will mark the first attempt to correct the faulty HBB gene in a patients own cells with non-viral delivery of CRISPR/Cas9 gene correction tools.

The four-year study will evaluate the safety and effectiveness of a single dose of CRISPR_SCD001 in up to nine patients with severe SCD, ages 1235, who will be recruited at UCLA and Benioff Childrens Hospital Oakland.

If the therapy is found to be safe in the first six treated patients, all adults, the trial will proceed to enroll three adolescents, ages 1218, to evaluate its safety in younger patients.

This therapy has the potential to transform sickle cell disease care by producing an accessible, curative treatment that is safer than the current therapy of stem cell transplant from a healthy bone marrow donor, Walters said.

If this is successfully applied in young patients, it has the potential to prevent irreversible complications of the disease, he added.

Donald Kohn, MD, the principal investigator at the UCLA trial site and who will oversee all therapy manufacturing for the study, said that in theory, gene therapy and gene-editing approaches should be much safer than a transplant from another person and could become universally available because they eliminate the need to find the needle in a haystack that is a matched stem cell donor.

Kohn, who has also been involved in the development of several gene therapies for other diseases, is a distinguished professor of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA and a member of the UCLA Broad Stem Cell Research Center.

It is noteworthy that this new trial comes from a consortium of not-for-profit academic institutions incentivized with a long-term vision to cure the disease with an affordable solution that can globally benefit everyone who needs it, said Fyodor Urnov, PhD, IGIs director of technology and translation, who will oversee the trials bioinformatics and genomics activities.

Marta Figueiredo holds a masters in evolutionary and developmental biology and a PhD in biomedical sciences from the University of Lisbon, Portugal. Her research is focused on the role of several signaling pathways in thymus and parathyroid glands embryonic development.

Total Posts: 50

Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells cells that made up the lining of blood vessels found in the umbilical cord of newborns.

Read more here:
1st CRISPR Gene Editing Trial Slated to Open in Severe SCD Patients - Sickle Cell Anemia News

In a long-term follow-up of an early-phase trial examining CD19.28 chimeric antigen receptor (CAR) T-cell therapy, the use of consolidative allogeneic hematopoietic stem cell transplant (alloHSCT) was associated with long-term and durable disease control in children and young adults with B-cell acute lymphoblastic leukemia (B-ALL).

These results were based on a cohort of 20 patients who were initially treated in a dose-escalation part of a phase 1 trial (NCT01593696) examining anti-CD19 CAR T-cell therapy in patients between 1 and 30 years who have not responded to standard treatment, plus an additional 30 patients who were treated in an expansion portion. The median follow-up for all patients examined was 4.8 years and represents the longest time period examined for the use of this therapy in children and young adults with B-ALL.

We demonstrate that CD19.28 CAR T cells followed by a consolidative alloHSCT can provide long-term durable disease control in [child and young adult patients] with relapsed or refractory B-ALL, wrote the study investigators who were led by Nirali N. Shah, MD. Following alloHSCT, we observed a significant long-term [event-free survival (EFS)] with an apparent plateau and a low relapse rate, providing support for this sequential approach for long-term cure.

The complete response rate (CR) was 62.0%, with 28 of the 31 patients achieving this end point also reaching minimal residual disease (MRD) negativity by flow cytometry. The rate of CR was higher in patients with primary refractory disease (P = .0035), fewer prior lines of therapy (P = .033), and an M1 marrow (P = .0007). Additionally, CR rates were better for patients who received fludarabine/cyclophosphamidebased lymphodepletion versus other regimens, at 69% and 25%, respectively (P = .041).

The median overall survival (OS) for the cohort was 10.5 months (95% CI, 6.3-29.2 months). The median EFS was 3.1 months (95% CI, 0.9-7.7), with rates at 3 and 6 months of 52.0% (95% CI, 37.4%-64.7%) and 38.0% (95% CI, 24.8%-51.1%), respectively. Notably, median EFS was not reached in patients treated with M1 marrow versus 0.9 months in those with M2 marrow (P .0001).

Of the patients achieving MRD-negative CR (n = 28), 21 (75.0%) went on to receive consolidative alloHSCT, with a median time to transplant of 54 days from infusion (range, 42-97). The median OS from transplant day 0 was 70.2 months (95% CI, 10.4 months-not estimable) and the median EFS was not reached. The rate of EFS at 5 years was 61.9% (95% CI, 38.1%-78.8%). There were 8 deaths between 0.8 and 71 months following alloHSCT, which included transplant-related complications and/or graft-versus-host disease or infection in 6 patients and 1 patient with a complication of secondary malignancy at 3 years post-transplant. Teo patients relapsed after alloHSCT, with a cumulative risk of relapse was 4.8% (95% CI, 0.3-20.3) and 9.5% (95% CI, 1.5%-26.8%) at 12 and 24 months, respectively, with death as a competing risk.

Of note, achieving a CR was associated with greater CAR T-cell expansion and grade 3/4 cytokine release syndrome (CRS). Overall, CRS occurred in 70.0% of patients, with 9 (18.0%) having a grade 3/4 event. Neurotoxicity occurred in 10 patients (20.0%), with 4 having severe neurotoxicity.

Central nervous system involvement was effectively treated with CAR T-cell therapy all patients with a marrow response and CRS, although 1 patients did have residual disease by flow cytometry at low levels.

The authors noted that given these findings, CD19-directed CAR T-cell therapy may be considered as a bridge to alloHSCT versus standard-of-care blinatumomab (Blincyto).

Despite its more ready availability, which is not dependent on manufacturing time or success thereof, the efficacy of blinatumomab in children is lower than in adults receiving blinatumomab and also lower than remission rates following CD19-CAR T cells, using any construct, particularly for those with high-burden disease, the study author wrote. Therefore, selection of CAR T cells over blinatumomab may be advantageous in patients with higher-burden disease and [extramedullary] disease or as a salvage for blinatumomab nonresponders.

References

Shah NN, Lee DW, Yates B, et al. Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL. J Clin Oncol. March 25, 2021. doi: 10.1200/JCO.20.02262

Originally posted here:
Transplant After CD19 CAR T-Cell Therapy Shows Durable Disease Control in Children, Young Adults With B-ALL - Cancer Network

Published on April 2, 2021

Recently, a 43-year-old man was presented at Fortis Hospital, Noida, complaining of severe back pain. Upon investigation, it was found that he was suffering from a rare disease, multiple myeloma which is a type of cancer that forms in the white blood cells or plasma cells. Here cancerous plasma cells accumulate in the bone marrow and crowd around the healthy blood cell that help in fighting infections by building antibodies, this puts the patients life at high risk. He therefore urgently required a Bone Marrow Transplant (BMT). Dr Rahul Bhargava, Director and Head, Hematology and Bone Marrow Transplant, Fortis Hospital, Noida and his team took a timely decision to go ahead with BMT to save his life.

A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Bone marrow is the soft, fatty tissue inside your bones. The bone marrow produces blood cells. Stem cells are immature cells in the bone marrow that give rise to different blood cells. Bone marrow transplant has now revolutionised. It is like a peripheral blood stem cell transplant, meaning, it is just like a blood transfusion (like platelet apheresis) which does not require any anesthesia.

Upon further investigation it was revealed that chemotherapy was required before BMT. Following the chemotherapy, on the 10thday of admission the team of doctors engulfed stem cells in the patients body which provided the body with a new source of healthy cells. Safe hospital environment and the doctors expertise in the area ensured that the BMT was done smoothly, without any complications and within 15 days the patient had been discharged. Usually, a patient takes 25-30 days to recover but here, due to patients will to recover and the facilities provided to him in the hospital he recovered at a faster pace.

Dr Rahul Bhargava, Director and Head, Hematology and Bone Marrow Transplant, Fortis Hospital, Noida, said,The case was complicated as the patient was suffering from high-risk multiple myeloma, which is a rare form of cancer. We took the necessary precautions and performed chemotherapy first to which he responded well and post that a Bone Marrow Transplant (BMT) was performed successfully. The process was smooth, and no complications arose during the same. We request patients to not fear BMT and undergo the process when required.

Talking about the clinical excellence at Fortis Hospital, NOIDA,Mr Hardeep Singh, Zonal Director, Fortis Hospital, Noidasaid, The team at Fortis Hospital, Noida try their best to save lives and do not give up even if there is 1% chance of survival. The patient was suffering from high-risk multiple myeloma for which immediate bone marrow transplant was required. The case was managed extremely well and with a lot of patience by Dr Rahul Bhargava and his team. I applaud the team of doctors for their continued commitment towards clinical expertise and patient care.

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Timely Bone Marrow Transplant by Fortis gives new lease of life to a patient with Multiple Myeloma - APN News

Actress Kirron Kher is suffering from Multiple Myeloma, a type of blood cancer. Read to know the causes, symptoms, treatment, risks and more about the fatal disease.

New Delhi | Jagran Health Desk:Kirron Kher is suffering from Multiple Myeloma which is a type of blood cancer. The actress's husband Anupam Kher made an official announcement about her illness through a post on his official social media handle.

He wrote,"Just so that rumours don't get the better of a situation Sikandar and I would like to inform everyone that Kirron has been diagnosed with multiple myeloma, a type of blood cancer. She is currently undergoing treatment and we are sure she weill come out of this stronger than before. We are are very blessed that she is being looked after by a phenomenal set of doctors. She's always been a figher and takes things head on. She's all heart nd that's why she has so many people that love her. So keep sending your love to her in your prayers and in your heart. She is well on her way to recovery and we thank everyone for their support and love. Anupam and Sikander."

What is Multiple Myeloma?

Multiple Myeloma is a progressive hematologic disease. It is a cancer of plasma cells, which are type of blood cells in the bone marrow. When cells multiply unconditionally, they crowd out normal cells, therefore the body does not work the way it should. This disease causes damage to the immune system, bones, red blood cells etc. Cancerous plasma cells gather in the bone marrow, produce abnormal proteins, which causes complications.

What are the symptoms of Multiple Myeloma?

When the disease is in its early stage there may be no signs of symptoms as such. But some of the visible symptoms of this disease are as follows:

Diagnosis of Multiple Myeloma

Doctors advise diagnostic tests considering many factors such as:

Tests of Multiple Myeloma

Here are some of the tests which are done for diagnosis of multiple myeloma:

Causes of Multiple Myeloma

Although the causes of myeloma are not very clear. But, the disease occurs when abnormal cells multiply rapidly, they accumulate and crowd out healthy blood cells. Abnormal antibodies (monoclonal protein or M proteins) produced by myeloma cells cause problems, such as damage to kidneys, bones etc.

Complications during Multiple Myeloma

Risk Factors ofMultiple Myeloma

Treatment ofMultiple Myeloma

Treatment of Multiple Myeloma includes medication, chemotherapy, radiation, corticosteroids, stem-cell transplant etc.

Posted By: Sanyukta Baijal

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Kirron Kher is suffering with Multiple Myeloma: Know the causes, symptoms and more about this type of blood cancer - Jagran English

The use of decitabine was linked to improved platelet counts and survival rates in patients with refractory prolonged isolated thrombocytopenia (RPIT), which can be a complication of allogeneic hematopoietic cell transplantation (HCT), according to the results of a study recently published in Blood Advances.

Isolated thrombocytopenia is a frequent and severe complication of HCT that is associated with worse outcomes, the study investigators explained in their report. According to the investigators, RPIT has been thought to relate to such factors as disease recurrence, treatment history, factors related to the transplant donor, and other transplantation complications. However, they suggested that the absence of a consistent definition for prolonged isolated thrombocytopenia has hindered understanding of its patterns.

This prospective, phase 3 clinical trial (ClinicalTrials.gov Identifier: NCT02487563) included patients who had undergone allogeneic HCT and developed RPIT and who were treated at any of 6 participating hematology centers in China.

Patients were randomly assigned across 3 treatment arms: low-dose decitabine with recombinant human thrombopoietin (arm A), decitabine only (arm B), or conventional treatment (arm C). Platelet response at 28 days following treatment was the primary study endpoint, and this was defined as a sustained increase of 30 x 109/L or more, independent of transfusion for 3 days.

Across the participating centers, 2616 allogeneic HCT recipients were identified, of whom 256 had developed thrombocytopenia for more than 60 days following transplantation, and 97 met criteria for study inclusion. A total of 91 patients were evaluated for response.

The response rate for arm A was 66.7%, for arm B it was 73.3%, and for arm C it was 19.4%. Arms A and B were not statistically different for response (P =.779), while the response rate for arm C was statistically lower than the others (P <.001).

At a median follow-up of 11 months, the estimated 1-year survival rates were 64.4% for arm A and 73.4% for arm B, which were both greater than in arm C (41.0%). When the decitabine arms were combined, the survival rate was 68.2%, which was significantly higher than 1-year survival in arm C (P =.008).

The treatment arms receiving decitabine also showed significantly elevated total megakaryocyte counts, platelet-shedding megakaryocytes, and megakaryocyte polyploidy, while arm C did not. This suggested there are improvements in megakaryocyte proliferation and maturation with decitabine, according to the investigators.

In conclusion, this multicenter randomized study demonstrates the efficacy and safety of decitabine for patients with RPIT after HCT, with improved response and prolonged survival, the study investigators wrote in their report.

Reference

Tang Y, Chen J, Liu Q, et al. Low-dose decitabine for refractory prolonged isolated thrombocytopenia after HCT: a randomized multicenter trial. Blood Adv. 2021;5(5):1250-1258. doi:10.1182/bloodadvances.2020002790

Read the original here:
Decitabine Improved Outcomes for Patients With Refractory Prolonged Isolated Thrombocytopenia - Hematology Advisor

Lake in the Hills Police Officer Mike Domagala with one of his children. | Provided Photo.

A Lake in the Hills police officer with 20 years of service, who is a father of four kids, says he will no longer be able to work as he battles a rare blood cancer, and a fundraiser has been started for him.

Mike Domagala began his law enforcement career in Fox River Grove in 2002. He was hired by the Lake in the Hills Police Department in 2012.

Domagala, 43, was diagnosed in July with multiple myeloma, which is a rare blood cancer that is not curable but is treatable.

According to the Mayo Clinic, cancerous plasma cells accumulate in the bone marrow and crowd out healthy blood cells. The cancer cells produce abnormal proteins that can cause complications.

Domagala is married and has four children, ages 5, 12, 16, and 23. At the onset of the cancer discovery, he had to have a pelvic biopsy, two bone marrow biopsies, blood work, PET scans, CT scans, and MRIs, according to a GoFundMe account.

Domagala has undergone multiple cycles of chemotherapy that started on August 4 and then a stem cell transplant in December.

He has not been able to patrol as an officer since his diagnosis. On March 25, Domagala said in an update that he had his 100-day post bone marrow appointment, which went well.

I also had my hematologist appointment for my maintenance therapy which will be a chemo pill every day and a bone healing transfusion once a month. The overwhelming support my family and I have received through this has been amazing and helps me continue to fight through this difficult time, he said.

Domagala said in February that he was optimistic about getting back to work. However, he said in his March 25 update that his doctor told him he would not be able to return to working the streets as a police officer.

I have been a police officer for almost 20 years and have always wanted to be since I was a child. I have no idea what I am going to do but I will figure it out as this is still sinking in, he said.

Fellow police officer Erik Watters started a GoFundMe account for Domagala in November and it continues to bring in donations from the public.

The fundraiser money is going towards uncovered medical expenses, travel expenses for treatments and to help his family with everyday expenses.

Mike maintains a strong fighting spirit and finds his strength in his love for his family. Mikes greatest concern is in continuing to provide for his family while he covers all of his uncovered medical expenses, Watter said.

The GoFundMe has a $50,000 goal and has raised $28,800 so far as of Thursday.

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Lake in the Hills police officer and father of 4 kids battling rare cancer forced to retire - Lake and McHenry County Scanner

The pancreas, saysGary Lewis, an endocrinologist at Toronto General Hospital and director of the Banting & Best Diabetes Centre at the University of Torontos Temerty Faculty of Medicine, is like an exquisitely sensitive and perfectly networked computer.

Second by second,he notes,the pancreassecretesjust the right amount ofinsulinor glucagontolower or raiseblood sugarintotheportal veinthat leadsdirectlyto the liver, the site of key metabolic processes. Insulingis then distributedto every tissue in the body via general circulation.

Thats one reason a cure for diabetes has proven elusive 100 years after the discovery of insulin.

Another big reason is the complexity of how the disease arises. In type 1 diabetes, the immune system destroys the insulin-producing beta cells of the pancreas, creating a life-threatening spike in blood sugar. Type 2 diabetes usually comes on more slowly, as the body becomes resistant to insulin or the pancreas cant produce enough of it.

Genetics play a role in both types. Exposure to viruses and other environmental effects may be a factor in type 1. Lifestyle factors, including weight gain and physical inactivity, are strongly linked to type 2.

The bottom line, says Lewis, is that diabetes is a multifactoral disease, and were not close to a cure.

Ask about treatments, though, and Lewis gets excited.

The last two decades have brought a plethora of clinical and research advances, from new drugs to boost and sensitize the body to insulin and promote weight loss, to lifestyle interventions that improve diet, continuous monitoring of blood sugar, long- and short-lasting insulin, better insulin pumps, pancreatic transplantsand pre-clinical stem cell and immunosuppressive therapies.

Progress on treatments has been fantastic, especially for type 2, Lewis says. Im very, very hopeful.

The distinction between treatment and cure in medicine is often unclear. And for the 3.6 million Canadians living with diabetes, the distinction matters less and lessif the goal is a full and healthy life.

Type 2 diabetes accounts for about 90 per cent of diabetes cases in Canada. Prevalence is rising, but Canadians with type 2 diabetes are living longer and have fewer diabetes-related complications.

The clinic doesnt look like it did 30 years ago, says Lewis, who mainly treats patients with type 2. We see fewer amputees, less blindness. Patients are generally healthier, and their prognosis is often excellent if they maintain their blood sugar target and other key parameters.

Weight loss is a cornerstone of treatments to lower blood sugar, and recent research has strengthened the link between weight reduction and type 2 diabetes management. Some people with type 2 can lose weight and control blood sugar through dietary changes and exercise alone.

Bariatric surgery is very effective for weight loss and often results in diabetes remission, although it comes with surgical risks and is expensive.

If we could prevent obesity, we could greatly reduce the incidence of type 2, Lewis says. And experiments have shown wecan get a remission withlifestyle changes, so we know what works.

The problem is broad implementation.

Ive tried to lose weight and I know how difficult it can be, especially in an environment of convenient and inexpensive calories, Lewis says. Moreover, factors such as income, education, ethnicity, access to healthy food and living conditions can make lifestyle changes that curb obesity nearly impossible.

Social determinants of health are overwhelmingly the most important influence on who gets type 2 diabetes, and how well or poorly they do with it, Lewis says.

Fortunately, dozens of new drugs for diabetes have hit the market in the last two decades.

Medications for weight loss round out the armamentarium, and some also protect against kidney damage and lower cardiac risk. Current therapies can reduce body weight up to 10 per cent, although a loss of 20 per cent or more would have a greater effect on outcomes for patients with type 2 diabetes, saysJacqueline Beaudry, an assistant professor of nutritional sciences at U of T who studies links between obesity, hormones and diet.

Beaudry is probing the biology that underpins these medications, including the gut hormones GLP-1 and GIP. They control blood glucose and reduce appetite, but scientists are unsure how.

If we could understand their mechanisms of action, we could design better drugs, Beaudry says.

For people with type 1 diabetes, continuous glucose monitors, insulin pumps and even automated closed-loopsystems that run on mobile apps to deliver insulin as-needed have radically changed the patient experience.

Sara Vasconcelos left),an assistant professor at U of Ts Institute of Biomedical Engineering, has worked withCristina Nostro (right), an associate professor in the department of physiology,and her team in the McEwen Stem Cell Institute at UHNto extend the survival and functionality of pancreatic precursor cells generatedfrom human stem cells.

Cell therapy could prove more liberating still.

University labs and biotechs are working on implantable devices that house insulin-producing cells derived from stem cells.

To that end,Cristina Nostro, an associate professor in the department of physiology in the Temerty Faculty of Medicine,and her team in the McEwen Stem Cell Institute at University Health Network recently discovered a more efficient way to generate and purify pancreatic precursor cells from human stem cells in the lab.

They have also found a way to vascularize those cells by working withSara Vasconcelos, an assistant professor at U of Ts Institute of Biomedical Engineering. Together, they have extended the survival and functionality of the cells in animal models of diabetes.

The biggest problem with these therapies is that the immune system rejects them. The same challenge currently hinders pancreas and islet transplants.

The immune system is an amazing machine, were luckyits so good, says Nostro. But its very difficult to control when it goes awry, as in autoimmune conditions.

Nostro is working with immunologists at the university on a method to protect insulin-producing beta cells from immune rejection, and she says many researchers in the field are now focused on immune-protective approaches.

Another strategy for type 1 diabetes is to tamp down the autoimmune response before the disease progresses. The idea is to prevent immune cells that damage the pancreas while the body still produces beta cells.

Groups around the world are bringing different ideas and creative approaches to treat type 1 diabetes, thats the beauty of science, says Nostro. I am very hopeful about what the future holds. Who knows? Maybe we will see hybrid technologies combining a pump and cells. We have to keep an open mind.

This story was originally published in U of T Med Magazines Insulin Issue.

Original post:
Insulin 100: How the road to a diabetes cure is yielding better treatments - News@UofT

Boxcar scars are a type of acne scars which look like round, oval depression. As the scars are of different types, for example, based on redness, depth or location, its treatment also varies. Microdermabrasion, Dermabrasion, Fillers, Chemical Peels, Laser Therapy, Microneedling, Punch Excision, and Subcision, are some of the treatments required for treating boxcar scars. As these scars cant go away of their own, People considering the treatment is growing.

Growing Preference for Micro needling and Ablative Lasers

The ablative lasers are considered as the gold standard for treating acne scars, patients have witnessed a 75% improvement in atrophic acne scars at 18 months after this high energy carbon dioxide laser treatment. The technique when used on dark skinned people showed good to excellent results in 74%, however hyper pigmentation was witnessed among 29% of patients. Due to its long time recovery process and various side effects, the ablative lasers have become less popular.

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Of late, microneedling is gaining momentum as they provide the best cosmetic outcomes. Due to its collagen inducing effect, the encouraging results prove that microneedling is an effective and inexpensive method for dealing with boxcar scars. It takes very less time for recovering, a study found that only after 3 treatments, patients can visibly see the positive effect in their scarring and is relatively risk free. Microneedling can be performed with a dermaroller or a microneedling pen. Microneedling involves puncturing the skin multiple times using needles, a tattoo gun or roller. When microneedling is combined with platelet rich plasma or glycolic acid peels, improvement in acne scar improved up to 62%.

Emerging Technologies Can Boost Adoption of Boxcar Scar Treatment

Researchers and scientists are always on the motion of developing and introducing new and more effective treatments for replacing the traditional therapies. For instance, a latest technology for the treatment of scarring is laser speckle contrast imaging (LSCI). LSCI helps in detecting the backscatter which eventually detects the blood flow by illuminating the tissue with its coherent laser light. The technique is relevant for scarring because the healing process of scarring requires adequate tissue perfusion. LSCI can also be used to treat patients with burn wounds as it detects the severity of partial thickness in wounds.

Complications in Laser Therapy

Side effects due to laser therapy such as burns, dyspigmentation and infection may happen after the laser treatment. Laser treatment has a risk of overheating the tissue through excessive heat generation or by a failure of the cooling techniques. The risk of burns is higher for lasers that use a continuous beam. Risk of dyspigmentation is higher in dark skinned or tan individuals. Due to such side effects, the treatment by laser may go back scale. However, latest innovations in the sector may help in mitigating the issue.

Competitive Landscape

The key players in the market include Merz, Inc., Cerave, Lumenis, Enaltus LLC, Scarsheal, Inc., CCA Industries, Proactiv Company, Cynosure, Inc., PCA Skin, Solta Medical, Smith and Nephew plc, Scarheal, Inc., NewMedical Technology, Inc., Bausch Health, Suneva Medical, Inc., Sonoma Pharmaceuticals, Inc., etc.

Latest development by doi.org shows 755nm picosecond Alexandrite laser has been effective in patients with acne scars. In the split face study, people were treated with laser in half of their face and that half showed effective improvement results in Post inflammatory erythema and acne scars. Patients stated that treatment was tolerable, with only mild erythema discovered as a side effect.

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A study reported in the Journal of cosmetic dermatology in February 2020 by Darrow Stem Cell Institute demonstrated that platelet rich plasma shows better response, fewer side effects, and shorter downtime as compared to combined subcision and PRP. The experiment was performed on 45 patients with atrophic acne scars by dividing the group into 3 and giving intradermal injection to first group, chemical reconstruction of skin scars was performed on second group and combined skin needling and PRP was performed on the third group. The third group witness significant improvement without any major side effect thus, reaching to the conclusion that PRP is beneficial for acne scars.

PICOCARE 450 is a US FDA approved machine developed by WonTech for laser skin care treatment. The innovative machine is responsible for treating all skin types, show faster visible results in less sitting. The technology targets only the pigment to be removed and is suitable for treating chickenpox scars, ice pink scars, boxcar scars, acne scars, etc.

Regional Outlook

According to WHO, scars affect almost 80-90% of teenagers in the western world. As per the study by National Library of Medicine, boxcar scars are prevalent and is almost in 54% population as post acne scar. Thus, rising incidences of burn cases and also increasing prevalence of boxcar scar cases is expected to drive the market during the forecast period. According to the survey by Harris Poll around 10 million patients who have had dermal filler have experienced filler treatment a good option, thus, its demand is also one of the factor for the boost of boxcar scar market.

Asia Pacific is also leading market for the boxcar scar treatment. Due to increased incidences of burns in India having a record of 70lakh burn injury cases every year, the adoption of treatment is also expected to surge. Rising awareness about the treatment of scars is yet another factor boosting the growth. Japan in Asian region is an ideal market due to availability of various treatment options owing to the increase in health care expenditure.

UK is a major contributor to the European market. According to British Association of Plastic, rising number of plastic surgery units in UK is fuelling the adoption of large number of incidences. Microneedling as a treatment is escalating in Europe owing to its benefits for skin tightening, better skin texture, scar reduction, improved skin tone, etc. Moreover, growing adoption of anti-ageing procedures, and awareness regarding the treatments is escalating the market further.

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Segmentation

By Treatment Type

By Laser Product

By End-user

By Region

Key Questions Answered

Carbon dioxide and Pulse dyed laser are some of the laser products used for boxcar scar treatment

Proactiv Company, Cynosure, Inc., PCA Skin, Solta Medical, Smith and Nephew plc, Scarheal, Inc., NewMedical Technology, Inc., Bausch Health, etc.

Latest innovations, growing awareness regarding the treatment, and comfortable treatment is giving people the confidence to treat.

US, UK, France, Germany and Italy are some of the largest markets for boxcar scars

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Boxcar Scars Market |Exclusive Report on Latest Trends and Market Growth Opportunities - BioSpace

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 that the European label for KEYTRUDA, Mercks anti-PD-1 therapy, be updated to include data from KEYNOTE-361, a Phase 3, open-label trial that evaluated KEYTRUDA as a monotherapy and in combination with chemotherapy for the first-line treatment of certain patients with advanced or metastatic urothelial carcinoma. In Europe, KEYTRUDA is approved for the treatment of adult patients with advanced or metastatic urothelial carcinoma (bladder cancer) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 with a Combined Positive Score (CPS) 10. This approval was based on a single-arm study, KEYNOTE-052; KEYNOTE-361 was conducted as part of a post-marketing commitment following the initial approval of KEYTRUDA for these patients.

As previously announced, KEYNOTE-361 did not meet its primary endpoints of progression-free survival (PFS) and overall survival (OS) for the combination of KEYTRUDA plus chemotherapy. However, the CHMP concluded that the benefit-risk profile remains positive and that including data from KEYNOTE-361 in the label allows physicians to evaluate the potential benefit-risk of KEYTRUDA on an individual basis.

KEYTRUDA has become an important treatment option for certain patients with locally advanced or metastatic bladder cancer in the European Union and other countries around the world, said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. We are pleased with todays positive opinion by the CHMP, which fulfills our post-marketing requirement for KEYTRUDA in these patients in the European Union and will enable continued access for patients in need of another treatment option.

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 1,400 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.

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 locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

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%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

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Merck Receives Positive EU CHMP Opinion for Updated Label of KEYTRUDA (pembrolizumab) To Include Results of Phase 3 KEYNOTE-361 Trial in Certain Adult...

NEW YORK, March 31, 2021 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (the Company or BeyondSpring) (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, today announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and the China National Medical Products Administration (NMPA) for use of plinabulin in combination with granulocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia (CIN). Plinabulin in combination with a G-CSF therapy, which received breakthrough therapy designation from the U.S. FDA and the China NMPA for concurrent administration with myelosuppressive chemotherapeutic regimens in patients with non-myeloid malignancies for the prevention of CIN, has the potential to raise the standard of care in CIN for the first time in 30 years.

CIN remains a severely unmet medical need. Treatment or prevention of CIN with G-CSF has been the standard of care since Neupogen was approved in 1991. The main benefit of G-CSF treatment, however, is in Week 2 after chemotherapy. Week 1 after chemotherapy is considered the neutropenia vulnerability gap where over 75% of CIN-related clinical complications occur, including febrile neutropenia, infection, hospitalization and death. Plinabulin is the first agent seeking FDA approval that has the potential to fill this gap by working in Week 1 to prevent the onset and progression of CIN. Therefore, combining plinabulin and G-CSF may maximize the protection of patients for the full cycle of chemotherapy, as demonstrated in the PROTECTIVE-2 Phase 3 registration study.

CIN is a major concern for physicians and their patients undergoing cancer treatment. Plinabulin provides benefits above and beyond what is currently available on the market and has the potential to be a game-changer for patients undergoing chemotherapy treatment, said Dr. Douglas Blayney, Professor of Medicine at Stanford University Medical School and global PI for CIN studies. CIN, which can lead to life-threatening infections, is the number one reason for the 4Ds in chemotherapy (Decrease, Delay and Discontinue dose and Downgrade regimen). We hope plinabulin will allow patients to better tolerate chemotherapy, thus enabling patients to stick to their optimal treatment plan and avoid serious CIN complications.

The NDA submission is based on positive data from BeyondSprings PROTECTIVE-2 Phase 3 registration study which showed that plinabulin in combination with pegfilgrastim demonstrated superior CIN prevention benefit, compared to pegfilgrastim alone. The study met the primary endpoint, with a statistically significant improvement in the rate of prevention of grade 4 neutropenia (improved from 13.6% to 31.5%, p=0.0015) and met all key secondary endpoints, including duration of severe neutropenia (DSN) and absolute neutrophil count (ANC) nadir. In addition, the combination reduced clinical complications such as incidence and severity of febrile neutropenia (FN) and incidence and duration of hospitalization for FN patients. The combination is well tolerated, with an over 20% reduction of grade 4 Treatment-Emergent Adverse Events (TEAE) in the combination compared to that of pegfilgrastim alone. The NDA submissions will include five supportive trials that show consistent CIN prevention in various chemotherapy regimens and cancers in over 1,200 patients.

This NDA submission is the culmination of years of research to prove that plinabulin can improve the long-established standard of care and address an unmet medical need to further alleviate the risk burden of CIN for patients receiving chemotherapy, said Dr. Lan Huang, co-founder, CEO, and chairman of BeyondSpring. With CIN responsible for potentially delaying treatment and causing life-threatening infections, we hope that receiving the improved care represented by the plinabulin and G-CSF combination will allow patients to better tolerate chemotherapy and potentially see increased treatment success rates. We are grateful for the patients participation in plinabulins clinical trials and the participation and contributions of our investigators and our many other clinical partners.

Each year in the U.S., 110,000 patients receiving chemotherapy are hospitalized after developing CIN, a severe side effect that increases the risk of infection with fever (also called febrile neutropenia, or FN), which necessitates ER/hospital visits. Due to the COVID-19 pandemic, the updated National Comprehensive Cancer Network (NCCN) guidelines expanded the use of prophylactic G-CSFs, including pegfilgrastim, from high-risk patients only (chemo FN rate >20%), to include intermediate-risk patients (FN rate between 10-20%), to reduce the number of hospital/ER visits related to CIN. The revision of the NCCN guidelines effectively increases the addressable market of patients who may benefit from treatment with plinabulin, if approved, to approximately 440,000 cancer patients in the U.S. annually.

There is a large unmet medical need and a growing market for CIN prevention and treatment in China as well. According to Lancet Oncology, 60% of East Asia cancer patients are treated with chemotherapy1. In 2020, there were 4.6 million new cancer patients in China which could correspond to 2.8 million patients using chemotherapy and needing CIN prevention agents. According to IQVIA data, the G-CSF drug market (for CIN treatment) in China is growing at over 30% a year.

About PROTECTIVE-2 (Study 106) Phase 3 Registration Study The Phase 3 portion of PROTECTIVE-2 was a double-blind and active-controlled global registration study. It was designed as a superiority study to compare the safety and efficacy of plinabulin (40 mg, Day 1 dose) + pegfilgrastim (6 mg, Day 2 dose) versus a single dose of pegfilgrastim (6 mg, Day 2 dose) in patients with breast cancer, treated with docetaxel, doxorubicin and cyclophosphamide (TAC, Day 1 dose) in a 21-day cycle. TAC is an example of high FN risk chemotherapy and is the regimen used in all G-CSF biosimilar registration studies.

The primary endpoint was the rate of prevention of Grade 4 neutropenia and secondary endpoints included DSN and mean ANC nadir in Cycle 1. Literature shows that despite the use of pegfilgrastim, 83 to 93 percent of patients treated with TAC still suffer Grade 4 neutropenia (or rate of Grade 4 neutropenia prevention at 7-17%), which demonstrates the severe unmet medical need for improved treatment2,3.

The ANC data, which are used to calculate these endpoints, were obtained through central laboratory assessments by Covance Bioanalytical Methods using standardized and validated analytical tests. Covance was the clinical contract research organization (CRO) for patient recruitment and monitoring of global sites for this study.

About CINChemotherapy-induced neutropenia (CIN) is the primary dose-limiting toxicity in cancer patients who receive chemotherapy and is the primary cause for the 4Ds (Decrease, Delay, Discontinue dose and Downgrade regimen). The 4Ds lead to a decrease of the anti-cancer benefit of chemotherapy, e.g., >15% of dose reduction correlated to >50% survival reduction4. The National Comprehensive Cancer Network (NCCN) recently updated its treatment guidelines for CIN prophylaxis using G-CSFs to include both high- and intermediate-FN risk patients treated with chemotherapies, to preserve hospital and ER resources for COVID-19 patients, and to maximize protection from CIN. The NCCNs action effectively doubled the number of patients recommended to receive CIN prophylaxis.

About PlinabulinPlinabulin, BeyondSprings lead asset, is a selective immune-modulating microtubule-binding agent (SIMBA). A global Phase 3 clinical trial in CIN (PROTECTIVE-2) with plinabulin in combination with pegfilgrastim versus pegfilgrastim alone has been completed and is the basis for an NDA filing in the U.S. and China for the prevention of CIN. In this trial, plinabulin reduced the neutropenia vulnerability gap associated with G-CSF therapy alone. Additionally, a global Phase 3 study for the treatment of later-stage NSCLC in EGFR wild-type patients (DUBLIN-3) is now fully enrolled and will evaluate the combination of plinabulin and docetaxel versus docetaxel alone for overall survival in NSCLC patients. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells5,6 and the second is early-onset action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs)7. Effects on HSPCs could explain the potential for plinabulin not only to prevent CIN but also to increase circulating CD34+ cells in patients. As a pipeline in a drug, plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1 / PD-L1 antibodies.

About BeyondSpringHeadquartered in New York City, BeyondSpring is a global biopharmaceutical company focused on developing innovative immuno-oncology cancer therapies to improve clinical outcomes for patients who have high unmet medical needs. BeyondSprings first-in-class lead asset plinabulin is a pipeline in a drug. It is filed for approval in the US and China for the prevention of chemotherapy-induced neutropenia (CIN) and has a fully enrolled pivotal study to test an anti-cancer benefit with an overall survival primary endpoint in non-small cell lung cancer (NSCLC). Additionally, it is being broadly studied in combination with various immuno-oncology agents that could boost the effects of PD-1 / PD-L1 antibodies. In addition to plinabulin, BeyondSprings extensive pipeline includes three pre-clinical immuno-oncology assets and a subsidiary, SEED Therapeutics, which is leveraging a proprietary targeted protein degradation drug discovery platform.

References:

Investor Contact:Ashley R. RobinsonLifeSci Advisors, LLC+1 617-430-7577arr@lifesciadvisors.com

Media Contact:Darren Opland, Ph.D.LifeSci Communications+1 646-627-8387darren@lifescicomms.com

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BeyondSpring Announces Submission of New Drug Application to US FDA and China NMPA for Plinabulin and G-CSF Combination for the Prevention of...

Leukemia is a type of cancer that affects the blood and bone marrow, where blood cells are formed. All types of leukemia cause rapid, uncontrolled growth of abnormal bone marrow and blood cells.

The main differences between the types include how fast the disease progresses and the types of cells it affects.

There are four main types of leukemia, which we describe in detail below:

Lymphocytic leukemia affects the lymphocytes, a type of white blood cell. Myeloid leukemia can affect the white blood cells, red blood cells, and platelets.

According to the National Cancer Institute, roughly 1.5% of people in the United States will receive a leukemia diagnosis at some point.

In this article, explore the four main types, their symptoms, the treatment options available, and the outlook.

The full name of this type of cancer is acute lymphocytic leukemia, and acute means that it grows quickly. Lymphocytic means that it forms in underdeveloped white blood cells called lymphocytes.

The disease starts in the bone marrow, which produces stem cells that develop into red and white blood cells and platelets.

In a healthy person, the bone marrow does not release these cells until they are fully developed. In someone with ALL, the bone marrow releases large quantities of underdeveloped white blood cells.

There are several subtypes of ALL, and the subtype may influence the best course of treatment and the prognosis.

One subtype is B-cell ALL. This begins in the B lymphocytes, and it is the most common form of ALL in children.

Another subtype is T-cell ALL. It can cause the thymus, a small organ at the front of the windpipe, to become enlarged, which can lead to breathing difficulties.

Overall, because ALL progresses quickly, swift medical intervention is key.

As research from 2020 acknowledges, healthcare providers still do not know what causes ALL. It may occur due to genetic factors or exposure to:

Although genetic factors may play a role, ALL is not a familial disease.

Learn more about ALL here.

ALL is the most common form of leukemia in children.

The risk of developing it is highest in children under 5 years old. The prevalence slowly rises again in adults over 50.

ALL symptoms can be nonspecific difficult to distinguish from those of other illnesses.

They may include:

In a person with AML, the bone marrow makes abnormal versions of platelets, red blood cells, and white blood cells called myeloblasts.

The full name of this disease is acute myeloid leukemia, and acute refers to the fact that it is fast-growing.

It forms in one of the following types of bone marrow cell:

Doctors classify AML by subtype, depending on:

AML can be difficult to treat and requires prompt medical attention.

Learn more about AML here.

The most common risk factor is myelodysplastic syndrome, a form of blood cancer that keeps the body from producing enough healthy blood cells.

Other factors that increase the risk of developing AML include:

Most people who develop AML are over 45. It is one of the most common types of leukemia in adults, though it is still rare, compared with other cancers.

It is also the second most common form of leukemia in children.

Symptoms of AML can vary and may include:

CLL is the most common form of leukemia among adults in the U.S. and other Western countries.

There are two types. One progresses slowly, and it causes the body to have high levels of characteristic lymphocytes, but only slightly low levels of healthy red blood cells, platelets, and neutrophils.

The other type progresses more quickly and causes a significant reduction in levels of all healthy blood cells.

In someone with CLL, the lymphocytes often look fully formed but are less able to fight infection than healthy white blood cells. The lymphocytes tend to build up very slowly, so a person might have CLL for a long time before experiencing symptoms.

Learn more about CLL here.

Genetic factors are the most likely cause. Others might include:

CLL is rare in children. It typically develops in adults aged 70 or over. However, it can affect people as young as 30.

CLL typically causes no early symptoms. When symptoms are present, they may include:

Also, 5090% of people with CLL have swollen lymph nodes.

CML is a slow-growing type of leukemia that develops in the bone marrow.

The full name of CML is chronic myeloid leukemia. As the American Cancer Society explain, a genetic change takes place in the early forms of the myeloid cells, and this eventually results in CML cells.

These leukemia cells then grow, divide, and enter the blood.

CML occurs due to a rearrangement of genetic material between the chromosomes 9 and 22.

This rearrangement fuses a part of the ABL1 gene from chromosome 9 with the BCR gene from chromosome 22, called the Philadelphia chromosome. The result of this fusion is called BCR-ABL1.

BCR-ABL1 produces a protein that promotes cell division and stops apoptosis, the process of cell death, which typically removes unneeded or damaged cells.

The cells keep dividing and do not self-destruct, resulting in an overproduction of abnormal cells and a lack of healthy blood cells.

This occurs during the persons lifetime and is not inherited.

CML typically affects adults. People aged 65 and older make up almost half of those who receive a CML diagnosis.

The symptoms of CML are unclear, but they may include:

The symptoms may vary, depending on the type of leukemia. Overall, a person should get in touch with a doctor if they experience:

Learn more about the symptoms of leukemia here.

Treatment for ALL typically involves three basic phases: induction, consolidation, and maintenance. We describe these in detail below.

Treatment for AML involves the first two phases. The induction phase may include treatment with the chemotherapy drugs cytarabine (Cytosar-U) and daunorubicin (Cerubidine) or idarubicin (Idamycin). The doctor may also recommend targeted drugs.

The goal of this phase is to kill the leukemia cells, causing the cancer to go into remission, using chemotherapy.

The doctor may recommend:

People having chemotherapy may need to see their doctors frequently and spend time in the hospital, due to the risk of serious infections and complications.

This phase of the treatment lasts for about 1 month.

Even if the treatment so far has led to remission, cancer cells may be hiding in the body, so more treatment is necessary.

The consolidation phase may involve taking high doses of chemotherapy. A doctor may also recommend targeted drugs or stem cell transplants.

This phase, consisting of ongoing chemotherapy treatments, usually lasts for 2 years.

Since CLL tends to progress slowly, and its treatment can have unpleasant side effects, some people with this condition go through a phase of watchful waiting before starting the treatment.

For a person with CML, the focus is often on providing the right treatment for the phase of the illness. To do this, a doctor considers how quickly the leukemia cells are building up and the extent of the symptoms. Stem cell transplants can be effective, but further treatment is necessary.

Overall, the initial treatment tends to include monoclonal antibodies, targeted drugs, and chemotherapy.

If the only concern is an enlarged spleen or swollen lymph nodes, the person may receive radiation or surgery.

If there are high numbers of CLL cells, the doctor may suggest leukapheresis, a treatment that lowers the persons blood count. This is only effective for a short time, but it allows the chemotherapy to start working.

For people with high-risk disease, doctors may recommend stem cell transplants.

A persons prognosis depends on the type of leukemia.

Learn more about survival rates for people with leukemia here.

About 8090% of adults with ALL experience complete remission for a while during treatment. And with treatment, most children recover from the disease.

Relapses are common in adults, so the overall cure rate is 40%. However, factors specific to each person play a role.

The older a person is when they receive an AML diagnosis, the more difficult it is to treat.

More than 25% of adults who achieve remission live for 3 years or more after treatment for AML.

A person may live for a long time with CLL.

Treatments can help keep the symptoms under control and prevent the disease from spreading. However, there is no cure.

Stem cell transplants can cure CML. However, this treatment is very invasive and is not suitable for most people with CML.

The United Kingdoms National Health Service estimate that 70% of males and 75% of females live for at least 5 years after receiving a CML diagnosis.

The earlier a person receives the diagnosis, the better their outlook.

Leukemia is a type of cancer that affects the blood and bone marrow. It can affect people of all ages.

There are four main types of leukemia. They differ based on how quickly they progress and the types of cells they affect.

Treatments for all types of leukemia continue to improve, helping people live longer and more fully with this condition.

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Types of leukemia: Prevalence, treatment options, and prognosis - Medical News Today

BKV can cause severe complications in immunocompromised transplant patients. Higher BKV DNA levels can often be present in urine prior to plasma, serving as an early predictor of an impending infection. A urine sample stabilised in cobas PCR Media allows the integrity of urine results to be maintained, making storage and transportation simpler without the need for sample refrigeration.

"Transplant patients face a number of significant challenges, including complications that can arise from viruses like BKV," said Ann Costello, Head Roche Diagnostic Solutions. "With the FDA clearance of this non-invasive and easily collectable sample type, we now offer choices for clinicians using a standardised, automated solution to routinely monitor and manage infection risks. Together with our viral load tests for Cytomegalovirus and Epstein-Barr virus, we are committed to bringing better care to transplant patients."

The cobas BKV Test runs on the widely available, high-throughput cobas 6800/8800 Systems. It is also approved for use in CE markets with EDTA plasma and urine stabilised in cobas PCR Media as sample types.

About the cobas BKV TestThe cobas BKV Test is a real-time polymerase chain reaction (PCR) test with dual-target technology that provides quantitative accuracy and guards against the risk of sequence variations that may be present in the BK virus. The cobas BKV Test has robust coverage with a limit of detection of 21.5 IU/mL and an expanded linear range from 21.5 IU/mL to 1E+08 IU/mL in EDTA plasma. Urine stabilised in cobas PCR Media has a limit of detection of 12.2 IU/mL and a linear range from 200 IU/mL to 1E+08 IU/mL.

The test offers an alternative to lab-developed tests (LDTs) or Analyte Specific Reagent (ASR) combinations, potentially minimising variability and complexity in testing, reducing workload and alleviating risk for laboratories. The test supports the goal of result standardisation across institutions by providing reproducible, high-quality results for clinical decision-making.

The fully automated cobas BKV, cobas CMV and cobas EBV Tests can run on the cobas 6800/8800 Systems simultaneously, providing absolute automation with proven performance and flexibility, leading to time savings and increased efficiency.

About BK polyomavirusBK polyomavirus (BKV) is a member of the polyomavirus family that can cause transplant-associated complications including nephropathy in kidney transplantation and hemorrhagic cystitis in hematopoietic stem cell transplantation. Infection can occur early in life, often with no symptoms. After primary infection, the virus can remain inactive throughout life, only to possibly reactivate in immunocompromised individuals, such as patients who receive solid-organ transplants. For kidney transplant patients, BKV infection is considered the most common viral complication, causing polyomavirus nephropathy (PVN) in up to 10 percent of kidney transplant recipients, and about 50 percent of PVN-affected patients will experience transplant graft failure.2 BKV is also associated with hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.3

About the cobas 6800/8800 SystemsWhen every moment matters, the fully automated cobas 6800/8800 Systems offer the fastest time to results with the highest throughput and the longest walk-away time available among automated molecular platforms. With proven performance, absolute automation and unmatched flexibility delivering unparalleled throughput 24/7 cobas 6800/8800 Systems are designed to ensure a lab's long-term sustainability and success now, more than ever. Learn more now: http://www.cobas68008800.com

About RocheRoche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people's lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world's largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the twelfth consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2020 employed more than 100,000 people worldwide. In 2020, Roche invested CHF 12.2 billion in R&D and posted sales of CHF 58.3 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit http://www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References[1] Jha V. Post-transplant infections: An ounce of prevention. Indian J Nephrol. 2010;20(4):171-178.[2] Jamboti, J. S. (2016) BK virus nephropathy in renal transplant recipients. Nephrology, 21: 647 654. doi: 10.1111/nep.12728. [3] Hirsch HH, Randhawa PS; AST Infectious Diseases Community of Practice. BK polyomavirus in solid organ transplantation-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13528. doi:10.1111/ctr.13528

Media Contact:

Elizabeth BaxterRoche Molecular Solutions Media Relations[emailprotected] 925.523.8812

Mike WeistUS Media RelationsRoche Diagnostics Corporation[emailprotected]317.371.0035

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http://www.roche.com

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Roche receives first FDA clearance for urine sample type for BK virus quantitative test to aid in the improvement of care for transplant patients -...

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