Ibrutinib for Chronic Pulmonary Graft-Versus-Host-Disease after Progression on Prior Therapy

Introduction: Chronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Pulmonary cGVHD consists of both obstructive and restrictive pulmonary changes, and as such, represents a broad spectrum of disease. While corticosteroids are a mainstay of treatment, there is no established standard-of-care for second line therapy. The Bruton's tyrosine kinase inhibitor ibrutinib was recently approved for treatment of cGVHD after failure of 1 or more lines of systemic therapy. However, the role of ibrutinib in patients with pulmonary cGVHD is not well understood. Here we report an institutional experience of ibrutinib as non-first-line therapy for pulmonary cGVHD. Methods: We performed a retrospective study of adult patients with steroid-dependent or steroid-refractory pulmonary cGVHD treated with ibrutinib as non-first line therapy between 2014 and 2018. Patients were diagnosed with pulmonary cGVHD if they met the 2014 National Institutes of Health cGVHD Consensus Panel criteria or were diagnosed based on expert opinion. All patients received appropriate GVHD prophylaxis at the time of transplant. The severity of pulmonary cGVHD was assessed by pulmonary function testing (PFT) done prior to and 180 days after initiation of ibrutinib therapy. The primary clinical outcome was absolute change in the percentage of predicted forced expiratory volume in 1 second (%FEV1) over 180 days. Patients were identified as having a complete response (normalization of %FEV1), partial response (≥10% increase in %FEV1), stable disease (