OBJECTIVES: Patients with steroid-refractory (SR) chronic graft-versus-host disease (cGVHD) are exposed to increased morbidity and mortality. This study aimed to systematically review the available clinical trials to investigate the efficacy of systemic treatments on response in patients with SR cGVHD.

METHODS: A systematic review of studies published in English between 2005 and 2017 was performed using Scopus and Cochrane Central Register of Controlled Trials. The review was limited to phase 2 to 4 clinical trials that used the National Institute of Health Consensus Criteria for diagnosing cGVHD and determining response, and included >25 patients per study arm. Data on response were extracted from the included trials.

RESULTS: Four phase 2, single arm trials were included. These investigated the efficacy of ibrutinib (n=1), interleukin-2 (IL-2; n=1), imatinib (n=1), and rituximab (n=1). Most trials failed to report response at a fixed time point; complete response [CR] and partial response [PR] data presented below are maximum response rates at any time during the follow-up. At median follow-up of 13.9 months, CR with ibrutinib was 21% (9/42 patients) and PR was 45% (19/42 patients). During 1 year follow-up, CR with rituximab was 22% (8/37 patients) and PR was 65% (24/37 patients). Patients treated with IL-2 or imatinib had no CR. By week 12, 61% of patients (20/33 patients) treated with IL-2 had PR. During 6 months, PR with imatinib was 51% (20/39 patients). The definitions of SR cGVHD varied in the included trials.

CONCLUSIONS: Findings suggest that patients with SR cGVHD treated with ibrutinib and rituximab can reach CR. None of the included trials reported comparative data demonstrating superior efficacy in response for one particular agent over others. Heterogeneity in the definition of SR cGVHD and follow-up time did not allow direct comparison of results. Further controlled clinical trials with larger cohorts are needed.