REACH-2 Trial of Ruxolitinib in Steroid-Refractory Acute GVHD

Transcript:

Corey Cutler, MD, MPH, FRCPC: REACH-2 was a randomized phase 3 study done for patients who had steroid-refractory acute graft versus host disease [GVHD]. It built upon the positive data and the positive experience from the REACH-1 study, which demonstrated activity of ruxolitinib in steroid-refractory acute graft versus host disease. REACH-2 randomized individuals to either ruxolitinib at a dose of 10 mg twice daily or best available therapy. In this trial, investigators had to declare what their best available therapy would be from among a list of 8 to 10 available therapeutics. That list included drugs such as antithymocyte globulin, mesenchymal stromal cells where available, methotrexate, mycophenolate mofetil, an mTOR inhibitors such as everolimus or sirolimus, etanercept or infliximab, and one had to stick to that list. Individuals were started on either their best available therapy or ruxolitinib, and then were evaluated for the usual end points of interest, such as overall response rate. Here, the primary end point of the trial, which was overall response rate at day 28, was found to be significantly higher in the ruxolitinib arm than the best available therapy arm. In the ruxolitinib arm, the rate of response was 62% in comparison to 39% in the best available therapy arm. Of the 62%, overall, 34% had a complete response, while the remaining 27% had a partial response. In the best available arm, the response of 39% was split evenly between complete and partial responders.

I think what’s very important to note about this trial is at day 56, which was representative of the durable overall response rate, unfortunately, a full third, if not higher, of the patients on ruxolitinib had lost their response by only 4 weeks later. At this point the response rate was under 40%, at 39.6%. Whereas the best available therapy response rate had similarly fallen from 30% at day 28 to only 22% by day 56. What this tells us is that while ruxolitinib is certainly more effective than that best available therapy list of agents, it is not the panacea because a significant portion of our patients actually require additional therapy beyond day 28.

The other important thing to mention is that the response rate for ruxolitinib was highest for patients who had steroid-refractory grade 2 GVHD, where it was 51% at day 28. That response rate fell dramatically for patients with a grade 3 or 4 disease, and it was only 20% among the 30 patients who had a grade 4 acute GVHD that was primary steroid-refractory. So there is still significant amount of work to be done in steroid-refractory acute graft versus host disease. There are a number of agents that are being tested in the scenario, and we wait to see the results of those clinical trials to know what the next best drug might be. Currently, ruxolitinib is the only agent that is actually approved for steroid-refractory acute graft versus host disease.

Transcript edited for clarity.