The Food and Drug Administration on December 15 approved the first-ever drug used for the prevention of acute graft-versus-host disease (aGVHD) in adult and pediatric patients, opening the door to safer bone marrow and blood stem cell transplants in patients who are not have a perfectly matched graft donor.
The FDA approved the use of Orencia (abatacept) — a drug already approved for the treatment of rheumatoid arthritis — in combination with a calcineurin inhibitor (CNI) and methotrexate (MTX), based on data from a multicenter study that included several researchers from Winship played lead roles.
“This is a game changer for our patients,” said one of the study’s senior investigators, Amelia Langston, MD, “especially for our African-American and mixed heritage patients who often cannot find a perfectly matched donor because they are underrepresented in the population. donor registry.” Langston is professor and vice chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine and director of the Bone Marrow and Stem Cell Transplant Program at Winship.
Other Winship researchers on the research team included Drs. Muna Qayed and Benjamin Watkins of the Atlanta Department of Pediatrics and Child Health Care. The principal investigator of this multicenter study was Leslie S. Kean, MD, PhD, a former Winship investigator and faculty member at Children’s Healthcare of Atlanta, and currently director of the Stem Cell Transplant Center at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.
“We are proud that the preclinical work and the first human pilot study conducted at Winship formed the basis for the development of abatacept in this setting and eventual FDA approval for this indication,” said Suresh S. Ramalingam, MD, executive director of Winship and the Roberto C. Goizueta Chair of Cancer Research, Emory University School of Medicine. “The strong collaboration between pediatric and adult oncologists at Winship has been the foundation of this success. Our commitment to improving the lives of cancer patients by conducting innovative, team-based research is illustrated by this achievement.”
What is aGVHD?
Acute GVHD occurs when a donor’s immune cells attack the host’s tissues. It can occur in up to 50% of patients who have received a stem cell transplant from a matched sibling. It is even more common when the donor is unmatched. Acute GVHD can be fatal after stem cell transplantation when the immune cells of the donor (the graft) see the body of the recipient (the host) as foreign and the donated cells attack the body.
“Acute graft-versus-host disease can affect different parts of the body and become a serious complication after transplantation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Onclogic Diseases in the FDA Center for Drug Evaluation and Research. “By potentially preventing the disease, more patients can successfully undergo bone marrow or stem cell transplants with fewer complications.”
Study shows lower rates of severe GVHD and better overall survival in those who received Orencia
The study leading to Orencia’s approval for the prevention of GVHD involved a double-blind, placebo-controlled study of 186 patients undergoing stem cell transplantation from an HLA-matched unrelated donor and randomized to receive Orencia or a placebo in combination with standard immunosuppressants. Patients assigned to Orencia had a lower rate of severe (grade III-IV) acute GVHD (6.8% for Orencia vs. 14.8% for placebo), and this translated into an improvement in both overall and severe acute GVHD-free survival for patients receiving Orencia.
In a separate arm of the study, patients who received transplants from a partially mismatched unrelated donor were all assigned Orencia in addition to standard immunosuppressants, and their results were compared with historical controls from the Center for International Bone Marrow Transplant Registry receiving standard immunoprophylaxis. . In this mismatched group, only 2.3% of patients receiving Orencia developed severe acute GVHD, compared to 30.2% of historical control patients.
There was a dramatic effect of Orencia on survival without severe GVHD at 6 months (97.7% versus 58.7%) as well as on overall survival at two years (73.6% versus 45.3%). Taken together, these results support the usefulness of Orencia in the prevention of severe acute GVHD and death in the unrelated donor transplant setting, especially when the donor is partially HLA mismatched.
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