Pirfenidone for the treatment of bronchiolitis obliterans syndrome related to chronic graft-versus-host disease.

Bronchiolitis obliterans syndrome (BOS) is a severe form of chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic cell transplantation (HCT) with five-year survival of 40%. Currently, there is no curative therapy for BOS. Pre-clinical data suggest that pirfenidone, an anti-fibrotic drug, may benefit small airway fibrosis in HCT-associated BOS. A single-arm, open-label, 56-week phase 1 trial with 56-month extension evaluated pirfenidone's tolerability, safety, and efficacy in BOS patients. Efficacy was measured using pulmonary function tests (PFT), quantitative CT (qCT) scans, patient reported outcomes (PRO), cGVHD indices, and laboratory tests. Lung function trajectory was assessed by change in regression slopes before and during treatment. Baseline qCT metrics, including percentage normal lung, air trapping, volume change (Jacobian), and heterogeneity of volume change (Jacobian variance) were analyzed by participant response. Among 30 participants, 25 completed the 56-week trial, and 10 continued into the extension. Overall, 63% tolerated the recommended dose without safety concerns. There was significant improvement in the percent predicted forced expiratory volume in 1 second (P=0.00267) when analyzing all participants and improvement in individual PFT trend for 41.3% of participants. Quantitative CT analysis by lobe showed healthier lungs in the upper lobes of responders. Significant improvements were noted in liver function tests, PRO related to physical functioning and shortness of breath, and cGVHD skin indices. These findings indicate that pirfenidone is safe and tolerable in BOS patients post-HCT and may improve lung function and symptoms. Further trials are warranted to evaluate the efficacy of pirfenidone as a treatment for BOS after HCT. (NCT03315741).