Safety and Efficacy of Belumosudil for Steroid-Resistant Chronic-Graft-Versus-Host Disease: A Systematic Review

Chronic graft-versus-host disease (cGVHD) remains a significant challenge after allogeneic hematopoietic cell transplantation. Although corticosteroids are commonly used as the first-line treatment, a substantial number of patients either do not respond adequately or suffer from considerable side effects; there is a need for more effective and better-tolerated alternatives. Belumosudil, a selective ROCK2 inhibitor, has shown encouraging potential in this context; however, detailed and comprehensive data regarding its effectiveness and safety are still limited. This systematic review evaluates the clinical efficacy, safety, and corticosteroid-sparing effects of belumosudil in cGVHD patients who have failed prior therapies. Following PRISMA 2020 guidelines, we systematically searched in PubMed, Embase, Scopus, Web of Science, and the Cochrane Library to identify studies evaluating the use of belumosudil in cGVHD. Six studies, including clinical trials and observational studies, encompassing a combined cohort of 315 patients, were included. Outcomes measured were overall response rate (ORR), complete and partial responses (CR/PR), duration of response (DOR), failure-free survival (FFS), overall survival (OS), incidence of adverse events (AEs), and steroid reduction. Belumosudil had an ORR of 46.7-85.7%, with partial responses predominant (PR: 70-85.7%). The median time to response was 4.1-5 weeks, with 6-month FFS ranging from 73 to 76%. Reduction in Corticosteroid dose was seen in 28.9-67% of patients, with discontinuation in up to 26%. Organ-specific responses were observed in the joints/fascia (25-80%), mouth (19-66.7%), and skin (14-40%). Adverse events were mostly mild to moderate, with 17.8-27% discontinuation rates. Belumosudil is an effective and well-tolerated treatment for refractory cGVHD, with fast responses, sustained disease control, and significant steroid-sparing effects. Its novel mechanism involving the inhibition of inflammation and fibrosis offers an important therapeutic alternative, although additional research and further comparative and long-term studies are required.

The online version contains supplementary material available at https://doi.org/10.1007/s12288-025-02298-z.