Clinical response to belumosudil in bronchiolitis obliterans syndrome: a combined analysis from 2 prospective trials.

Chronic graft-versus-host disease (cGVHD) of the lung, or bronchiolitis obliterans syndrome (BOS), is a high-risk disease manifestation associated with poor outcomes. Currently available treatments have demonstrated limited clinical efficacy in this setting. Belumosudil is a novel oral selective ROCK2 inhibitor which was recently FDA approved in the treatment of cGVHD. We identified 59 subjects with BOS who were enrolled and treated on two prospective clinical trials of belumosudil. Patients with BOS had a % predicted forced expiratory volume in 1 second (%FEV1) of 79% at enrollment and clinician attribution of lung disease due to cGVHD. The NIH cGVHD lung score at enrollment were 1 (n=30, 59%), 2 (n=23, 39%), or 3 (n=6, 10%). According to NIH response criteria, the best overall response rate (ORR) for lung cGVHD was 32% (partial response: 17%; complete response: 15%). Response rates were inversely proportional to baseline NIH GVHD lung score at enrollment (lung score 1: ORR 50%; lung score 2: ORR 17%, lung score 3: ORR 0%) (p=0.006). In multivariable analysis, male sex, lower baseline NIH cGVHD lung score, and partial response to previous line of cGVHD therapy prior to enrollment were associated with higher rates of lung-specific response. No significant correlation was identified between pulmonary function evaluations and measures of patient symptoms (NIH lung symptom score or Lee Symptom Scale score for lung). In conclusion, belumosudil treatment was associated with lung-specific clinical responses for subjects with BOS, which were more commonly observed in less advanced disease. Optimization of treatment response evaluations remains a challenge in patients with BOS.