REACH-3 Trial of Ruxolitinib in Steroid-Refractory Chronic GVHD

Transcript:

Corey Cutler, MD, MPH, FRCPC: REACH-3 was a trial designed very similar to REACH-2; this was a randomized controlled trial where individuals were randomized to receive ruxolitinib at a dose of 10 mg twice daily or best available therapy. The list of best available therapy compounds in this study was somewhat different than the acute GVHD [graft versus host disease] trial. While some things like extracorporeal phototherapy, methotrexate, and mycophenolate were common, here, individuals could receive ibrutinib, imatinib, rituximab as additional agents in the best available therapy arm. The most commonly prescribed best available therapy agents in REACH-3 were extracorporeal phototherapy as well as mycophenolate. This was a 300-plus person trial, which really enrolled only adults; there were a small number of individuals aged between 12 and 18. An important distinction here, particularly as it relates to the definitions of chronic steroid-refractory GVHD, is that a significant portion of patients were allowed to be enrolled based on the lack of response after only 1 week of therapy of corticosteroids, which to me, is a little bit premature, except for patients who are progressing very rapidly in front of our eyes. Approximately 40% of subjects were enrolled based on that.

The primary end point was the response at week 24. The response in the ruxolitinib arm was approximately double that of the response in the best available therapy arm. Nearly 50% of subjects had responded, almost entirely with partial responses, as is expected in chronic graft versus host disease, versus 25.6% in the best available therapy arm. The primary end point was an assessment at week 24; however, the best overall response rate was collected. In the ruxolitinib arm it was 76% vs 60% in the best available therapy arm. I think there are 2 important things to note about that. No. 1, the best overall response is significantly higher, suggesting that once again, the durability of responses is low, or not quite what we want with ruxolitinib. I think the entire field was quite surprised that the best overall response to best available therapy was as high as 60%. That was actually very intriguing.

Some other important findings from this trial looked at things like failure-free survival and duration of response. Here there was a significant advantage in the duration of response as well as the failure-free survival between ruxolitinib and best available therapy. To me, the failure-free survival could not be evaluated beyond 6 months because there was an allowed crossover at the 6-month point. I don’t think that the data are terribly interpretable. There was separation of curves before the 6-month mark favoring the ruxolitinib arm quite nicely. As expected, there was a fairly high incidence of any grade of anemia or thrombocytopenia with ruxolitinib. These are on-target expected adverse effects. So 20% to 30% of subjects had either anemia or thrombocytopenia. A significant portion, 12% to 15%, actually had grade 3 or higher anemia or thrombocytopenia. Subjects who have low counts coming into ruxolitinib therapy might require dose modifications.

Transcript edited for clarity.