Ruxolinitib As Salvage Therapy For Chronic Graft-Versus-Host Disease

Background: Chronic graft-versus-host disease (cGVHD) remains a common and potentially life-threatening complication after allogenic hematopoietic stem cell transplantation (HCT). Systemic corticosteroids are first-line therapy, however, they are often associated with inadequate responses and multiple side effects. There has been no single standard therapy for refractory cGVHD. Recently, ruxolitinib, a selective JAK1/2 inhibitor, has been suggested to have efficacy as salvage therapy in cGVHD. However, data are limited to a multi-center retrospective survey of 41 patients (Zeiser et al. Leukemia. 2015; 29(10):2062-8). Herein, we present a single-institution9s experience with ruxolitinib as salvage therapy for management of refractory cGVHD. Methods: In this single-center, IRB-approved, retrospective analysis, the charts of 47 patients who received ruxolitinib as salvage therapy for cGVHD from March 2016 through December 2016 were reviewed. Clinical data were collected and analyzed at start of ruxolitinib treatment, 3 months-post, and 6 months-post to identify changes in prednisone dose, patient perceived improvement, physician perceived improvement, and incidence of adverse events including hospitalizations, documented infections, cytopenias, relapse, and death. In addition, we assessed for treatment failure-free survival (FFS) from the time of ruxolitinib to any of the following events: initiation of new cGVHD therapy, relapsed disease, patient death, or discontinuation of ruxolitinib. Results: The cohort consisted of 47 patients (median age = 51; range = 21 - 91; 21 females and 26 males) who received fully ablative (n=26) or reduced-intensity conditioning (n=18) followed by an allogeneic HCT from matched related donor (n=15), unrelated donor (n=13), or other donor sources (cord or haplo-identical donors: n=16) for their hematologic disorders. The median time from HCT to ruxolitinib initiation was 40.5 months (range: 3.8 to 267.2). Of the 47 patients in this cohort, 38 patients (80.9%) had sclerotic chronic graft versus host disease. The average dose of prednisone in evaluable patients was 11.1 mg/day (95% CI 6.9 - 15.3 mg/day) at time of ruxolitinib initiation, which decreased to 7.7 mg/day (95% CI 4.1 - 11.4 mg/day, p=0.043 by paired signed rank test, 30% reduction) at 3 months, and 5.6 mg/day (95% CI 3.2 - 8.0, p Conclusion: Ruxolitinib is associated with prednisone reduction after 3 and 6 months, self-/physician-reported improvements, and favorable FFS at 6 months in patients with steroid-refractory chronic GVHD. Prospective randomized trials are warranted to further define its therapeutic benefits and risks of cytopenia/infectious complications. Disclosures Salhotra: Kadmon: Consultancy.