Efficacy and safety of belumosudil for refractory chronic graft-versus-host disease in routine practice

TL;DR

Belumosudil shows promising results in treating chronic graft-versus-host disease when other therapies fail.

Contribution

This study evaluates belumosudil's efficacy and safety in real-world cGVHD patients who failed multiple therapies.

Findings

A 52% overall response rate was observed in patients with refractory cGVHD.

Median time to response was 2.1 months, with better outcomes in older patients and those with fewer prior therapies.

Concomitant ruxolitinib increased the likelihood of reducing immunosuppressants.

Abstract

Chronic graft versus host disease (cGVHD) affects 30–50% of allogeneic hematopoietic stem cell transplantation recipients, with those failing standard therapy including ruxolitinib constituting an important unmet medical need. We retrospectively analyzed the use of the ROCK2 inhibitor belumosudil in moderate to severe cGVHD that had failed ≥ 2 lines of systemic therapies, in order to evaluate its efficacy and safety in routine practice. Eighteen men and thirteen women at a median age of 50 (21–68) years with cGVHD (moderate, N = 12; severe, N = 19) that had failed a median of 3 (2–6) lines of systemic therapy were studied. Twenty-eight patients (90%) had failed prior ruxolitinib therapy, with seventeen patients (55%) continuing ruxolitinib despite unsatisfactory response. Among 29 patients evaluable, overall response rate was 52% (complete response:7%; partial response: 45%). Median time to response was 2.1 months (95% confidence interval, CI: 1.6–5.7), and was significantly shorter in patients older than 50 years (P = 0.008) and having received < 4 lines of therapy (P = 0.007). Median duration of response was 36.8 weeks (95% CI: 16.4 weeks to not reached). Median time to reduction of immunosuppressants by ≥ 50% was 6.7 months (95% CI: 2.3–12.2). Grade ≥ 3 adverse events occurred in 13% (4/31) of patients. Six patients (19%) discontinued treatment. At 12 months, overall survival and failure-free survival were 95% and 55%. Concomitant ruxolitinib significantly increased the probability of immunosuppressant reduction (P = 0.007). Belumosudil showed promising efficacy and safety in cGVHD patients in routine practice.

The online version contains supplementary material available at 10.1007/s00277-026-06760-4.

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