Nilotinib in SR/SD cGvHD: A systematic review and meta-analysis

Results from a systematic review and meta-analysis evaluating nilotinib in patients with steroid-refractory or -dependent (SR/SD) chronic graft-versus-host disease (cGvHD) were published in Transplant Immunology by Bahbah et al. Four prospective, single-arm, early-phase, interventional studies (N = 112) were included, with proportions pooled using random-effects meta-analysis. The primary objective was to determine the overall clinical efficacy of nilotinib, defined by the pooled overall response rate (ORR). 

Key data: The pooled ORR was 36% (95% confidence interval [CI], 13–59; I² = 84.9%); however, after omission of the sequential rituximab + nilotinib study, the ORR decreased to 24% (95% CI, 13–34; I² = 0%). Complete response (CR) and partial response (PR) rates were 8% (95% CI, 2–14; I² = 0%) and 32% (95% CI, 10–54; I² = 86.2%), respectively. Organ-specific responses were variable, with pooled ORRs of 58%, 36%, 28%, 27%, 26%, and 20% for gastrointestinal (GI), oral, skin, ocular, liver, and lung cGvHD, respectively. Treatment discontinuation due to adverse events (AEs) occurred in 26% of patients; Grade ≥3 upper or lower respiratory tract infections were the most frequent severe AE (17%). The certainty of evidence was very low for all outcomes. 

Key learning: Nilotinib demonstrated modest and heterogeneous efficacy in patients with SR or SD cGvHD, though high rates of intolerance and discontinuation may limit routine clinical utility. Any future role is likely to be restricted to carefully selected patients, ideally within biomarker-guided or dose-optimized protocols.