Salvage nintedanib plus low-dose ruxolitinib therapy for bronchiolitis obliterans syndrome refractory to calcineurin inhibitors and glucocorticoids after allogeneic transplantation

Bronchiolitis obliterans syndrome (BOS) is a severe pulmonary complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with limited therapeutic options once refractory to standard immunosuppression. We conducted a pilot study from January 2018 to December 2024, enrolling consecutive patients with BOS defined by NIH criteria who failed glucocorticoids and calcineurin inhibitors for ≥4 weeks. Sixteen patients received salvage therapy with ruxolitinib 5 mg twice daily and nintedanib 150 mg twice daily (RN cohort) in continuous 28-day cycles for up to six cycles, while 37 contemporary patients served as controls. At baseline, NIH lung scores in the RN cohort were 18.8% NIH 1, 18.8% NIH 2, and 62.5% NIH 3. The median number of treatment cycles was 3.5 (range, 1-6). At 3 months, 11 patients (68.8%) achieved ≥10% improvement in %FEV1 from baseline (median = 26.5%, range = 15.6%-58.2%). By NIH lung response criteria, the overall response rate (ORR) was 62.5% (12.5% complete response, 50.0% partial response) in the RN cohort versus 13.5% (5.4% complete, 8.1% partial) in controls. Notably, hematologic toxicities were less frequent with RN therapy than in controls. These findings suggest that low-dose ruxolitinib combined with nintedanib is an effective and well-tolerated salvage regimen for BOS after allo-HSCT and warrant confirmation in a prospective phase II study.