Systemic steroids are the standard first-line treatment for acute graft-vs-host disease (aGVHD), but approximately 50% of patients become steroid refractory or dependent (SR/D). Ruxolitinib is the only FDA and EMA approved therapy for patients with SR/D aGVHD. In the phase 3 REACH2 trial (NCT02913261), ruxolitinib demonstrated superior efficacy to best available therapy (BAT) in treating SR/D aGVHD, with significantly higher overall response rate (ORR) at day 28, durable ORR at day 56, and longer median overall survival. Identifying biomarkers and clinical characteristics associated with increased probability of response could guide treatment decisions. In this exploratory analysis of the REACH2 study, we developed baseline (pretreatment) and Day 14 models to identify patient characteristics and biomarkers (12 aGVHD-associated cytokines/chemokines, 6 immune cell types, and 3 inflammatory proteins) before and during treatment that affected the probability of response at day 28. Treatment with ruxolitinib versus BAT, type of conditioning, skin involvement, and age were strongly associated with increased likelihood of response in ≥1 model. Lower levels of most aGVHD and immune cell markers at baseline were associated with increased probability of response. In the Day 14 model, levels of aGVHD markers at day 14, rather than change from baseline, impacted probability of response. For both models, bias-corrected area under receiver operating characteristic (AUROC) values (baseline, 0.73; Day 14, 0.80) indicated high level of correspondence between fitted and actual outcomes. This first biomarker study in context of a randomized phase 3 aGVHD trial, highlights the potential prognostic value of select biomarkers and patient characteristics.
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