Baricitinib for treatment-refractory cGvHD: Results from a phase I/II study

Results from a single-center, phase I/II study (NCT02759731) evaluating the efficacy and safety of baricitinib in adults with severe, treatment-refractory chronic graft-versus-host disease (cGvHD; N = 24) were published in Blood Advances by Holtzman et al. Patients had received a median of 5 (range, 2–11) prior lines of therapy. The primary efficacy endpoint was the 6-month overall response rate (ORR) per the 2014 National Institutes of Health (NIH) cGvHD response criteria, assessed at 24 weeks (Day 1 of Cycle 7). Baricitinib was initiated at a dose of 2 mg daily and increased to 4 mg daily if no dose-limiting toxicity (DLT) was observed.

Key data: The ORR at 6 months was 76.2% (95% confidence interval [CI], 52.8–91.8). Responses were observed across all involved organs, with the highest response rates in the lower gastrointestinal (GI) tract (100%) and joints/fascia (91%), and the lowest in the skin (4%). Durable responses were observed in 93% of evaluable patients at 12 months. At a median follow-up of 35.8 months, median failure-free survival (FFS) was 19 months (95% CI, 11–26), with no relapses or deaths occurring during treatment. The most common Grade ≥2 adverse events (AEs) were viral upper respiratory infection (URI; 42%), hypophosphatemia (21%), and lung infection (21%). No DLTs at either dose level (2 mg or 4 mg) were observed. 

Key learning: In this study, baricitinib demonstrated durable, multiorgan efficacy and an acceptable safety profile in patients with severe, treatment-refractory cGvHD, supporting further evaluation in earlier-line and larger-scale studies.