Clinical considerations for ruxolitinib in the treatment of steroid-refractory acute graft-versus-host disease (GVHD) and steroid-refractory or -dependent chronic GVHD: a plain language summary.

Abstract

What is this summary about? Ruxolitinib (JAKAFI^®) is a Janus kinase (JAK) 1 and JAK2 inhibitor that is approved for acute and chronic graft-versus-host disease (GVHD). The phase III REACH2 and REACH3 trials tested efficacy and safety of ruxolitinib for patients with acute and chronic GVHD, respectively, who were no longer responding to steroids. This summary describes additional analyses from REACH2 and REACH3 that evaluated the effect of treatment initiation time, use of antifungal azole treatments, and development of cytopenias (low number of blood cells) on ruxolitinib effectiveness. What happened in the analyses? Results from REACH2 and REACH3 were analyzed to inform whether time to start treatment, use of azoles, and developing cytopenias affected how well ruxolitinib worked. Treatment effectiveness was measured as any response to treatment, including complete resolution of all GVHD symptoms. What were the results? When analyzing time to start treatment, more patients taking ruxolitinib had a better response than those taking control treatments, regardless of when treatment started. In acute GVHD, treatment responses generally appeared higher when ruxolitinib was started early (within 3 days of steroids not working). The effectiveness of ruxolitinib persisted even among patients taking azoles or for patients who developed cytopenias, with some patients having their dosage adjusted. What do the results mean? The treatment benefit of ruxolitinib compared with control treatments is consistently observed across patients with acute and chronic GVHD who no longer respond to steroids, regardless of time to start of treatment, use of azoles, or developing cytopenias. Dose modifications of ruxolitinib may need to occur to ensure treatment is well tolerated. ClinicalTrials.gov registration ID: NCT02913261 (REACH2) and NCT03112603 (REACH3).