The safety and efficacy of belumosudil and ruxolitinib combination in ruxolitinib refractory cGVHD

Despite advances with JAK and ROCK inhibitors, durable responses in chronic GVHD (cGVHD) remain challenging. For patients with advanced, multi-refractory disease, simultaneously targeting multiple pathways may be necessary. Building on preclinical synergy between JAK and ROCK inhibition, we evaluated the combination of belumosudil and ruxolitinib in a multicenter, retrospective study of 57 ruxolitinib-refractory cGVHD patients. The cohort had high-risk features, with 63.2% having severe NIH-grade disease and 66.7% receiving ≥ 5 prior lines of therapy.The primary endpoint was the 3-month overall response rate (ORR). At a median follow-up of 170 days, the ORR was 59.6%, with a best overall response of 75.4%. Notably, in patients with lung involvement (63.2%), 83.3% achieved symptom-based responses, versus 3.7% FEV1 improvement. The 12-month failure-free survival rate was 94.5%, and 86.4% of patients achieved a corticosteroid reduction. The regimen demonstrated a favorable safety profile, with only 5.3% grade ≥ 3 pneumonia and no treatment-related discontinuations or severe hematologic toxicities.These results confirm the clinically meaningful efficacy and safety of dual JAK/ROCK inhibition in this heavily pretreated population. These findings support the mechanistic rationale for concurrent pathway inhibition and warrant prospective validation in randomized controlled trials.