Belumosudil Mesilate

Belumosudil was approved by the Food and Drug Administration in the United States for the treatment of relapsed/refractory chronic graft-versus-host disease (cGVHD) based on a randomized phase 2 trial comparing 2 belumosudil doses. The efficacy and safety of belumosudil vs the best available therapy (BAT) has not been studied. Applying rigorous statistical methodology to real-world data, this study estimated the efficacy of belumosudil vs BAT in cGVHD patients whose disease failed to respond to 2 to 5 prior lines of therapy (LOTs). Retrospective data between March 2015 and 2024 were collected across 8 US sites for 196 patients, contributing 113 belumosudil and 245 BAT LOTs. The primary outcome was 6-month overall response rate (ORR), defined as the proportion of complete or partial responses based on 2014 National Institutes of Health consensus criteria, physician assessment, or corticosteroid dose taper of ≥50% without cGVHD progression. Death, relapse, and beginning a new LOT were considered a lack of response. Targeted maximum likelihood estimation (TMLE) was used to estimate the 6-month ORR following belumosudil vs BAT (38.7% vs 26.8%, respectively) or 44.2% improvement with belumosudil (1-sided 95% confidence interval [CI], [4.4 to ∞]; P = .031). TMLE was also used to estimate 1-year failure-free survival when treated with belumosudil (61.2%) or BAT (47.8%), a 13.5% difference (95% CI, 1.5-100; P = .032). Descriptive assessment of safety showed adverse events recorded in 27% of belumosudil and 36% of BAT LOTs. Findings demonstrated that belumosudil improved clinical outcomes compared to BAT in cGVHD patients with 2 to 5 prior LOTs, and safety was consistent with belumosudil’s established profile.