Real-world outcomes in refractory chronic graft-versus-host disease: the Italian multicenter experience with belumosudil

Chronic graft-versus-host disease (cGvHD) remains a major late complication of allogeneic hematopoietic stem cell transplantation, leading to impaired quality of life and late non-relapse mortality. Belumosudil, an oral ROCK2 inhibitor with immunomodulatory and antifibrotic properties, represents a novel treatment for steroid-refractory or -dependent cGvHD. We conducted a retrospective, multicenter study of 80 patients treated with belumosudil across 29 Italian transplant centers through a compassionate use program. Patients were heavily pretreated (74% with ≥3 prior lines, 84% previously exposed to ruxolitinib), with severe disease in 86% and a median of three organs involved. The best overall response rate was 62.5%, while overall response rates was 52.6%, 57.6%, and 55.0% at 3, 6, and 12 months, respectively. Median time to response was 3 months, and the 12-month duration of response was 83.4%. Failure-free survival at 12 months was 67.5%. Responses were observed in all involved organs. Patient-reported outcomes assessed through the NIH Severity Index Score (0–10 scale) showed meaningful improvements (≥-2 points) in 33%, 36%, and 29% of patients at 3, 6, and 12 months, respectively. Treatment was well tolerated. These real-world findings confirm the effectiveness of belumosudil in patients with cGvHD refractory to multiple lines of immunosuppressive therapy.