Efficacy and Safety of Belumosudil in Chronic Graft versus Host Disease (cGVHD): A Systematic Review and Meta-Analysis

Background Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation. Corticosteroids, despite being the first-line therapy, necessitate alternative treatments lacking standardized efficacy and having toxicity risks. Belumosudil, a selective ROCK2 inhibitor, offers a targeted approach for steroid-refractory cGVHD. This meta-analysis assesses efficacy and safety of Belumosudil in treating chronic cGVHD. Methods A comprehensive search was conducted through PubMed, Cochrane, Embase, and ClinicalTrials.gov databases from inception till January 24, 2025. The outcomes were pooled as untransformed proportions with 95% confidence intervals (CI) using the random-effects model. The I² and Cochran’s Q statistics were employed to evaluate interstudy heterogeneity. All calculations were performed using MetaXL. The risk of bias (ROB) was assessed using ROBINS-I. Results This meta-analysis included 5 studies with 302 patients. We found a significant pooled overall response rate (ORR) of 74% (95% CI: 69–79%, I² = 0%) in patients with cGVHD treated with belumosudil. There was a 14% complete remission rate (95% CI: 0.0–42%, I² = 96%), 70% partial remission rate (95% CI: 65–75%, I² = 0%), 21% treatment discontinuations (95% CI: 0–55%, I² = 97%) and 10% mortality (95% CI: 7–15%, I² = 0%). We found a pooled prevalence of 36% (95% CI: 26–46%, I² = 67%) for upper respiratory tract infections (URTI), 10% (95% CI: 7–13%, I² = 0%) for pneumonia, 33% (95% CI: 28–38%, I² = 0%) for diarrhea, and 30% (95% CI: 19–41%, I² = 75%) for nausea in patients receiving belumosudil. Conclusion Belumosudil shows effectiveness for steroid-refractory cGVHD, but study variability and safety concerns make conclusions uncertain. More robust trials with larger sample sizes and longer follow-ups are required to establish conclusive evidence.