Real-world Canadian data on belumosudil therapy in heavily pretreated patients with steroid-refractory chronic graft-versus-host disease: treatment outcomes and risk factor analysis for failure-free survival

Chronic graft-versus-host disease (cGvHD) remains one of the common causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Belumosudil (BEL), a selective ROCK2 inhibitor, has immunomodulatory and anti-fibrotic properties, offering a new therapeutic option. Real-world data (RWD) in heavily pretreated patients remain limited, particularly for combination of BEL with ruxolitinib (RUX). We conducted a multicenter, real-world study in 46 patients treated for refractory cGvHD with BEL under a Canadian compassionate program. Treatment outcomes were assessed using the NIH consensus response criteria for overall response rate (ORR), failure-free (FFS), overall survival (OS), and safety. Forty-six patients were included with a median follow-up of 11.4 months; the best ORR was 52% (n = 20/38). The FFS and OS rates at 12 months were 64.3% and 91.1%, respectively. Steroids were discontinued in 73% at 12 months. BEL combination therapy with RUX exhibited equivalent treatment outcomes to BEL monotherapy, although patients treated with drug combination presented with more advanced form of GvHD and mostly failed RUX therapy. A prognostic risk model based on prior acute GvHD and involvement of ≥ 4 organs effectively stratified FFS at 12 months: 100% with no risk factors, 75.8% with one, and 30% with two risk factors (HR 3.91, 95% CI 1.58-9.67, p = 0.003). BEL demonstrated durable efficacy and acceptable safety in heavily pretreated cGvHD. BEL treatment was associated with a high probability of corticosteroid withdrawal. Risk stratification by disease burden and prior aGvHD identified distinct prognostic groups, informing patient selection and future therapeutic strategies.