A phase 2 multicenter trial of ruxolitinib to treat bronchiolitis obliterans syndrome after allogeneic HCT

Bronchiolitis obliterans syndrome (BOS) occurring after allogeneic hematopoietic cell transplantation (HCT) is a high-risk manifestation of chronic graft-versus-host disease. In this prospective, multicenter phase 2 trial (ClinicalTrials.gov, NCT03674047), adult participants with BOS were treated with ruxolitinib 10mg twice daily, continuously in 28-day cycles for up to 12 cycles. Participants enrolled into newly diagnosed (<6 months since BOS diagnosis, cohort A) or established (≥6 months since BOS diagnosis, cohort B) disease cohorts, respectively. The primary objective was to evaluate the early treatment effect of ruxolitinib, assessed by the change in forced expiratory volume in 1 second (FEV1) at 3 months compared to enrollment. The primary endpoint differed according to cohort (Cohort A: improvement, defined as ³10% increase in FEV1; Cohort B: stabilization, defined as absence of ³10% decrease in FEV1). Between 2019 and 2022, 49 participants meeting criteria for BOS were enrolled and treated (cohort A, n=36; cohort B, n=13). The primary endpoint was achieved by 27.8% of participants with new BOS and 92.3% of participants with established BOS. According to the 2014 NIH Consensus Criteria, the best lung-specific overall response rate on ruxoltinib for the 49 participants was 34.7% (16.3% complete response, 18.4% partial response), with most responses occurring in mild or moderate disease. Non-infectious severe (grade ≥3) treatment-emergent adverse events were infrequent. Nine severe infectious events occurred and were largely respiratory in nature. These results support the use of ruxolitinib in the management of BOS after allogeneic HCT.