Winship Research Helps FDA Approval of First-Ever Acute GVHD Drug | Emory University

The Food and Drug Administration on Dec. 15 approved the first-ever drug to be used for the prevention of acute graft-versus-host disease (aGVHD) in adult and pediatric patients, opening the door to bone marrow transplants and safer blood stem cells in patients who do not have a perfectly matched donor transplant.

The FDA has approved the use of Orencia (abatacept) – a drug already approved for the treatment of rheumatoid arthritis – together with a calcineurin (CNI) and methotrexate (MTX) inhibitor, based on data from a multicenter study in which several Winship researchers played lead roles.

“It is a game-changer for our patients,” said one of the study’s lead investigators, Amelia Langston, MD, “especially for our African American and mixed heritage patients who often cannot find a perfectly matched donor because they are under-represented in the 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 study’s leadership team included Drs. Muna Qayed and Benjamin watkins from the Atlanta Department of Pediatrics and Children’s Health Care. The principal investigator of this multi-center study was Leslie S. Kean, MD, PhD, former Winship researcher and faculty member at Children’s Healthcare 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 initial human pilot trial conducted at Winship formed the basis for the development of abatacept in this setting and the eventual FDA approval for this indication,” said Suresh S. Ramalingam, MD, Executive Director of Winship and Roberto C. Goizueta Chair in Cancer Research, Emory University School of Medicine. “The strong collaboration between the pediatric and adult oncologists at Winship has been the basis of this success. Our commitment to improving the lives of cancer patients by conducting innovative research as a team is exemplified by this accomplishment. “

What is an aGVHD?

Acute GVHD occurs when immune cells from a donor attack the tissues of the host. It can occur in up to 50% of patients who have received a stem cell transplant from a matched sibling. It occurs even more often when the donor is not a match. Acute GVHD can be fatal after a stem cell transplant when the donor’s immune cells (the transplant) regard the recipient’s body (the host) as a foreigner and the donated cells attack the body.

“Acute graft-versus-host disease can affect different parts of the body and become a serious post-transplant complication,” said Richard Pazdur, MD, director of the FDA’s Center of Excellence in Oncology and Acting Director of the Bureau. of Oncologic Disease Center of the FDA. for drug evaluation and research. “By potentially preventing the disease, more patients can undergo successful bone marrow or stem cell transplants with fewer complications.”

Study shows lower rates of severe GVHD and better overall survival in people who received Orencia

the to study that led to Orencia’s approval for the prevention of GVHD included a double-blind, placebo-controlled trial involving 186 patients who underwent stem cell transplants from an unrelated HLA-compatible donor who received random Orencia or placebo in combination with standard immunosuppressive drugs. Patients assigned to Orencia had a lower rate of severe acute GVHD (grade III-IV) (6.8% for Orencia vs. 14.8% for placebo), which resulted in improved overall survival. and without severe acute GVHD for patients receiving Orencia.

In a separate arm of the study, patients undergoing a transplant from a partially incompatible unrelated donor were all assigned to receive Orencia in addition to standard immunosuppressive drugs, and their results were compared to historical controls from the Center for International. Bone Marrow Transplant Registry which received the standard immunoprophylaxis. In this unpaired group, only 2.3% of patients receiving Orencia developed severe acute GVHD, compared to 30.2% of historical controls.

There was a dramatic effect of Orencia on survival without severe GVHD at 6 months (97.7% vs. 58.7%), as well as on overall survival at two years (73.6% vs. 45.3%) . Taken together, these results support the utility of Orencia in the prevention of severe acute GVHD and death in unrelated donor transplantation, particularly when the donor is partially incompatible with HLA.


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