Real-World Experience Study of Belumosudil in Steroid-Refractory Chronic Graft-Versus-Host Disease (cGVHD) Demonstrated High Treatment Response without Significant Toxicities

Introduction cGVHD is a frequent complication of allogeneic HCT (allo-HCT) and is the main cause of late non-relapse mortality (NRM). Treatment failure to upfront therapy with corticosteroids is frequent. Belumosudil is an inhibitor of Rho-GTPase-associated coiled-coil kinase 2 (ROCK2) indicated for steroid-refractory (SR) or -dependent (SD) cGVHD. However, there is limited data since its FDA approval. Thus, we conducted a real-world experience study in a single high-volume transplant center. Methods We conducted a retrospective study evaluating 66 allogeneic hematopoietic cell transplantation (allo-HCT) recipients with SR/SD cGVHD treated with belumosudil from 03/2021 to 10/2023. A subset of patients who participated in the belumosudil phase 2 study were included in the analysis. Survival outcomes were calculated by Kaplan-Meier. Failure-free survival (FFS) was calculated from the time of belumosudil start until the event of treatment failure or latest follow up. Results The median age was 58 years (range 45-66) and 47 (71%) were male. Most patients received an unmodified PBSC graft and non-PTCY GVHD prophylaxis (Table). At the start of belumosudil treatment, the majority (85%) had moderate and severe cGVHD with multiorgan involvement. Most patients were previously treated with ruxolitinib, but treatment overlap occurred in 14 patients (21%) patients. Among evaluable subjects, the 6-month overall response rate (ORR) was 59% (CR 4.5%, PR 55%) whereas the 12-month ORR was 64% (CR 10%, PR 54%). A subset of patients achieved deeper responses with ongoing therapy at 12 months including those with 6-month stable cGVHD to PR (n=3, 4.5%), and stable or PR cGVHD to CR (n=3, 4.5%) (Fig. 1). With a median follow-up for survivors of 15 months, the 6 and 12 months FFS was 79% (95%CI: 70-90) and 72% (95%CI: 62-84), respectively (Fig. 2), and the median FFS was 20 months. The 6- and 12-month OS was 92% (95%CI: 86-99) (Fig. 3). No grade ≥3 toxicities were identified. The most common reason for treatment discontinuation was cGVHD progression, and none discontinued due to toxicities. Conclusion Belumosudil was associated with high treatment response and survival outcomes including FFS in patients with advanced cGVHD. Notably, deeper treatment responses were observed with ongoing therapy in a subset of patients. Treatment was overall well tolerated, and toxicity-related therapy discontinuation did not occur. Our real-world study indicates a similar experience to the clinical trial and supports the use of belumosudil in SR/SD cGVHD.