Post-Conference Perspectives: Advances in Chronic and Acute Graft-versus-Host Disease - Episode 2

Approval of Ruxolitinib: Steroid-Refractory Acute GVHD


Yi-Bin A. Chen, MD: The approval of ruxolitinib for steroid-refractory acute graft-versus-host disease was a major advance for several reasons. Ruxolitinib is an agent that is a JAK1, JAK2 inhibitor. It is not systemic broad immunosuppression as we have used in the past. It inhibits several inflammatory pathways that we believe to be important for the pathophysiology of graft-versus-host disease [GVHD]. It is also one of the newer drugs and one of the few that have been studied rigorously for graft-versus-host disease. First, based on preclinical mouse models by our colleagues, and then taken to robust clinical trials that have just been completed. REACH-1 was a single-arm, multicenter clinical trial enrolling patients who had steroid-refractory acute graft-versus-host disease. It enrolled 71 patients. Ultimately, the approval was judged on 49 patients who met the formal definition of being steroid refractory. Out of these 49 patients, 57% had an overall response by day 28. Thirty percent had a complete response by day 28. And these results compared very favorably to the outcomes of patients in the past and those of other agents.

Based on this trial, the FDA [US Food and Drug Administration] approved ruxolitinib for patients 12 years and older for the treatment of steroid-refractory acute [graft-versus-host disease]. Many of us have been excited by the use of ruxolitinib. It certainly has given our patients yet another option to try and treat this challenging disease. And we look forward to formally studying it further to show its role in graft-versus-host disease.

REACH3 is a multicenter randomized study that’s studying the role of ruxolitinib for steroid-refractory chronic graft-versus-host disease. Building on the momentum of using ruxolitinib for acute GVHD, many of us do feel there is a role for JAK inhibition in chronic graft-versus-host disease. REACH3 is a randomized study. Patients who are steroid refractory and enroll in the trial were then randomized to [receive] ruxolitinib versus the best appropriate therapy. The best appropriate therapy was at the discretion of the investigator from a list of agents that had been traditionally used for the treatment of steroid-refractory chronic graft-versus-host disease.

The primary end point of the trial was overall response rate at 6 months. If ruxolitinib has a role in chronic graft-versus-host disease, which many of us do feel it does, we hope to see a benefit in terms of response rate when using ruxolitinib. We hope to see patients who receive ruxolitinib were able to taper steroids faster, in those 6 months. And we also hope there’s improvement in long-term quality of life for these patients who receive ruxolitinib.

Transcript Edited for Clarity