Belumosudil for acute GVHD after allogeneic hematopoietic stem cell transplantation: a retrospective case series

Current therapies for acute graft-versus-host disease (aGVHD) are limited by suboptimal efficacy or excessive immunosuppression. In this retrospective, exploratory, hypothesis-generating case series, we evaluated belumosudil, a selective Rho-associated coiled-coil kinase 2 inhibitor, in eight patients with aGVHD. All patients had gastrointestinal involvement, and 62.5% had grade IV aGVHD. Seven patients (87.5%) had received prior systemic therapy, including Janus kinase inhibitors. At day 28, the overall response rate was 100%, with six patients (75.0%) achieving complete response. The median time to response was 13.5 days (range, 7-28). Responses were sustained through day 56 in evaluable patients (5/5 complete responders). At a median follow-up of 269 days (range, 25-335), the median failure-free survival was 123.5 days (95% CI, 30.0 to not estimable). No grade ≥3 treatment-related adverse events occurred. In one patient with post-transplant relapse, immunosuppressive agents were tapered to promote a graft-versus-leukemia (GVL) effect. This patient developed stage 4 skin and stage 1 gastrointestinal aGVHD that resolved with belumosudil, with subsequent minimal residual disease negativity and complete response. This exploratory case series suggests that belumosudil-based therapy may have activity in aGVHD, with possible GVL activity in one case, warranting further investigation.