Phase 2 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease

•Treatment with abatacept in steroid-refractory cGVHD was associated with a 58% ORR with all responders achieving a PR.•Treatment with abatacept was well tolerated and led to a durable reduction in prednisone dose. [Display omitted] Steroid-refractory chronic graft-versus-host disease (cGVHD) after allogeneic transplant remains a significant cause of morbidity and mortality. Abatacept is a selective costimulation modulator, used for the treatment of rheumatologic diseases, and was recently the first drug to be approved by the US Food and Drug Administration for the prophylaxis of acute graft-versus-host disease. We conducted a phase 2 study to evaluate the efficacy of abatacept in steroid-refractory cGVHD. The overall response rate was 58%, seen in 21 out of 36 patients, with all responders achieving a partial response. Abatacept was well tolerated with few serious infectious complications. Immune correlative studies showed a decrease in interleukin -1α (IL-1α), IL-21, and tumor necrosis factor α as well as decreased programmed cell death protein 1 expression by CD4+ T cells in all patients after treatment with abatacept, demonstrating the effect of this drug on the immune microenvironment. The results demonstrate that abatacept is a promising therapeutic strategy for the treatment of cGVHD. This trial was registered at www.clinicaltrials.gov as #NCT01954979. Despite the recent introduction of ruxolitinib and belumosudil into routine practice, management of patients with advanced chronic graft-versus-host disease (cGVHD) represents a major challenge. In this month’s CME article, Koshy et al report on the results of a phase 2 trial evaluating the T-cell immune modulator abatacept in cGVHD, demonstrating an overall response rate of 58% and a 3-year failure-free survival of 66% in patients with a median of 3 prior lines of therapy. Treatment with abatacept is well tolerated and leads to a durable reduction in prednisone dose, arguing for further evaluation of this drug alone and in combination in future studies.