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 transplant (HCT), with a 5-year survival rate of 40%. Currently, there is no curative therapy for BOS. Preclinical data suggest that pirfenidone, an antifibrotic 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 patients with BOS. Efficacy was measured using pulmonary function tests (PFTs), quantitative computed tomography (qCT) scans, patient-reported outcomes (PROs), 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. Of 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 = .00267) when analyzing all participants, and improvement in individual PFT trend for 41.3% of participants. qCT analysis by lobe showed healthier lungs in the upper lobes of responders. Significant improvements were noted in liver function tests, PROs related to physical functioning and shortness of breath, and cGVHD skin indices. These findings indicate that pirfenidone is safe and tolerable in patients with BOS after 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. This trial was registered at www.ClinicalTrials.gov as #NCT03315741.