FDA Approval Summary: Abatacept for the Prophylaxis of Acute GVHD.

In December 2021, the FDA approved abatacept (Orencia; Bristol Myers Squibb) in combination with a calcineurin inhibitor (CNI) and methotrexate (MTX) as the first drug for the prophylaxis of acute GVHD (aGVHD) in adult and pediatric (2 years of age and older) patients undergoing hematopoietic stem cell transplantation (HSCT) from a matched or one allele-mismatched unrelated donor (URD). Study IM101311 included a randomized (1:1), double-blind evaluation of abatacept (N = 73) versus placebo (N = 69) +CNI+MTX as aGVHD prophylaxis in patients ≥6 years undergoing an 8/8 HLA-matched URD HSCT. Overall survival and grade II-IV aGVHD-free survival at day 180 after transplantation for abatacept versus placebo showed HRs [95% confidence interval (CI)] of 0.33 (0.12-0.93) and 0.54 (0.35-0.83), respectively. A second study, IM101841, was conducted using real-world data from the Center for International Blood and Marrow Transplant Research registry for abatacept+CNI+MTX (N = 54) versus CNI+MTX (N = 162) in patients who underwent 7/8 mismatched URD HSCT. Day 180 overall survival was 98% (95% CI, 78-100) with abatacept+CNI+MTX versus 75% (95% CI, 67-82) with CNI+MTX. Serious adverse reactions included cytomegalovirus and Epstein-Barr virus reactivation. An additional study in patients 2 to <6 years of age was required as a condition of the approval.