Belumosudil in the Management of Heavily Pretreated Prolonged Chronic GVHD: A Retrospective Multicenter Real-World Study

Chronic graft-versus-host disease (cGVHD) is the primary contributor to morbidity and mortality following allogeneic stem cell transplantation (ASCT). Belumosudil, a ROCK2 inhibitor, was approved for the cGVHD treatment after at least two prior lines of systemic therapy, based on prospective data. The current study evaluated the real-world efficacy and safety of belumosudil across all major adult and pediatric SCT centers in Israel. This retrospective study included all consecutive patients with cGVHD treated with belumosudil via compassionate use programs at nine centers. Key baseline characteristics, ASCT details, and cGVHD features were collected from patients' electronic medical records. The analyzed outcomes encompassed overall response rate (ORR), glucocorticoid dose reduction, failure-free survival (FFS), and overall survival (OS). Data on the safety and tolerability of this therapy were also assessed. The cohort included 45 heavily pretreated (median of 4 prior systemic therapies) patients at a median age of 46 (range, 4–75) years. Severe cGVHD with multi-organ involvement was documented in 84.4% of patients. The ORR was 55.6% (n = 25), with 6.7% achieving complete response and 48.9% — partial response. The median time to the best response was 100 days. A significant reduction in the glucocorticoid dosage was observed, with the median dose decreasing from 0.29 mg/kg/day at baseline to 0.02 mg/kg/day at the last follow-up. The 6-month and estimated 12-month OS rates were 95% and 75%, respectively. The most common adverse event was pulmonary infections (17.8%); only one patient discontinued treatment due to an adverse event. Female sex was associated with a borderline statistically significant improvement in FFS. Results of this study demonstrate that belumosudil is effective and well-tolerated even in a heavily pretreated real-world patient population with severe and refractory cGVHD. The observed response rates, glucocorticoid dose reductions, and encouraging survival outcomes point to belumosudil as a crucial therapeutic option for this challenging condition.