On December 15, 2021, the FDA approved a new indication for abatacept (Orencia; Bristol Myers Squibb), a selective T-cell co-stimulation modulator, in combination with a calcineurin inhibitor and methotrexate, for the prophylaxis of acute graft-versus-host disease (GVHD) in adults and pediatric patients aged ≥2 years receiving hematopoietic stem-cell transplantation from a matched or 1 allele-mismatched unrelated donor. The FDA granted abatacept a priority review and breakthrough therapy and orphan drug designations.
Abatacept was previously approved for the treatment of polyarticular juvenile idiopathic arthritis and adult psoriatic arthritis and was initially approved in 2005 for the treatment of adult rheumatoid arthritis.
“Acute graft-versus-host disease can affect different parts of the body and become a serious posttransplant complication,” said Richard Pazdur, MD, Director, FDA’s Oncology Center of Excellence, and Acting Director, Office of Oncologic Diseases, FDA’s 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,” he said.
The approval for this new indication incorporated real-world evidence as a component of the clinical efficacy determination, according to the FDA. Two separate studies evaluated the safety and efficacy of abatacept plus immunosuppressant therapy for patients aged ≥6 years who received transplants from a matched or mismatched unrelated donor.
The first study included 186 patients who received transplantation from a matched unrelated donor. The researchers measured severe (grade 3-4) acute GVHD-free survival, overall survival, and moderate-severe (grade 2-4) acute GVHD-free survival 6 months after transplantation. Although severe acute GVHD survival was not significantly improved in patients who received abatacept (87%) compared with those who received placebo (75%), patients who received abatacept had a 97% overall survival rate compared with 84% for those who received placebo. For moderate-severe acute GVHD-free survival, patients who received abatacept had a 50% rate compared with 32% for those who received placebo.
The second study used real-world data from the Center for International Blood and Marrow Transplant Research to analyze outcomes of 54 patients treated with abatacept prophylaxis plus standard immunosuppressive drugs versus 162 patients who received standard immunosuppressive drugs alone. Results showed higher overall survival at 6 months after transplantation among those who received abatacept (98% vs 75%).
The most common (≥10%) adverse reactions associated with abatacept were anemia, hypertension, cytomegalovirus reactivation/cytomegalovirus infection, pyrexia, pneumonia, epistaxis, decreased CD4 lymphocytes, hypermagnesemia, and acute kidney injury.