Clinical Predictors of Response in Chronic Graft-Versus-Host Disease: Results From the "Predicting the Quality of Response to Specific Treatments (PQRST)" Trial.

Despite significant progress in chronic GVHD therapies, challenges remain in understanding pleomorphic phenotypes and varying responses to treatment. The aim of this study was to identify predictors of treatment response. We conducted a prospective, observational cohort study of patients beginning first-, second-, or third-line systemic therapy for chronic GVHD with defined agents. We describe best and 6-month response rates, failure-free survival (FFS), and clinical predictors of response. Best response rates were 60%-70% to index therapies, which subsequently declined to 40% at 6 months. Similarly, failure-free survival at 6 months was 66%, but dropped to 41% at 18 months and did not vary based on agent or line of therapy. No clear clinical predictors of FFS or survival were identified. Patient-reported fatigue was associated with NIH response, but we did not find any other clinical predictors of response. Six-month responders were associated with higher FFS at 1 year. When patients were responding to therapy, more than one organ improved. Conversely, one organ usually accounted for patients progressing. In the contemporary era, we demonstrate high but not durable responses across all agents and the first three lines of therapy. There remain large variations in practice, and no specific patterns of agents used, organ responsiveness, or overall responsiveness were identified. Additional study is needed to identify clinical and biologic phenotypes and define predictors of treatment response. Trial Registration: clinicaltrials.gov identifier: NCT04431479.