The REACH3 Clinical Trial of Ruxolitinib in Chronic GVHD
Yi-Bin Chen reviews data from the REACH3 trial of ruxolitinib in patients with chronic steroid-refractory graft versus host disease.
Transcript:
Yi-Bin Chen, MD: I’m going to talk a bit about ruxolitinib [Jakafi]. This is what we said we’d all use for our first patient. So ruxolitinib, what was approved recently for the treatment of steroid-refractory chronic graft-versus-host disease [GVHD], was approved back in, I believe, 2019 for the treatment of steroid-refractory acute graft-versus-host disease. But the approval for chronic was based on this phase 3 REACH3 study [NCT03112603] with Robert Zeiser [MD, Freiburg University Medical Center] as a first author published in Blood. This was a large international study of 329 patients with steroid-refractory chronic graft-versus-host disease who are 12 years or older. And patients were randomized 1:1 to either receive ruxolitnib 10 mg twice a day, or BAT, which is best appropriate therapy. So best appropriate therapy, as you can see from the slide, was a list of conventional options for chronic graft-versus-host disease that the treating provider could select from. And this is really the only practical way to do a randomized control study in graft-versus-host disease given the global differences in practice as to what people favored for the standard. The primary end point here was measured at 24 weeks, or 6 months, as overall response rate, the sum of complete response, and partial response. And the key secondary end points were the composite end point failure-free survival at as well as symptoms and symptom improvement measured by patient-reported outcomes.
These were the patients, and just to summarize they’re well balanced, and these are the patients you’d expect in a chronic graft-versus-host disease study. To qualify here, you had to have moderate-to-severe disease at enrollment, and most patients obviously had received steroids and some obviously steroids plus another agent during that time that they had received for prophylaxis. And here are the results. You can see the response rates, the add up PR [partial response] and CR [complete response] in the ruxolitinib arm, it was about 50% had an overall response rate at week 24, whereas in the BAT group, or the control group, it was around 25%. So about doubling in the overall response at 24 weeks. It should be highlighted here, and you’ll see that in other studies, that the CR rate here is 6.7%, and that’s what we see in chronic graft-versus-host disease, which is what was so compelling about the ibrutinib [Imbruvica] data albeit in a very small number with selected patients. If we look at best overall response, which is a little bit dirty by the fact that the BAT group was allowed to cross over to ruxolitinib, you can see that there is still a benefit to ruxolitinib about 76% versus 59% going forward. And then if we look at the key secondary end points here, failure-free survival, which is what was really impressive. Median time over a year and a half for the patients in the ruxolitinib group versus less than 6 months for those receiving best appropriate therapy. And that’s reflected in the duration of response you can see on your right.
The adverse events are what we’d expect. We knew from using ruxolitinib for other indications that there were probably going to be more hematological issues, specifically thrombocytopenia and anemia. And that is what was reflected compared to the control group. But for the rest of the adverse events that are somewhat listed on this slide, there was not much of a difference between best appropriate therapy and ruxolitinib. Ruxolitinib had an advantage here because many of us had used it for the treatment of myeloproliferative neoplasms, which it had been approved for long ago. And so, we were used to using it. Somewhat knew how to use it, and then saw the success in acute graft-versus-host disease. So, the uptake, for chronic GVHD, I think is certainly not surprising.
Transcript edited for clarity.
