An expert in hematology/oncology reviews study data and results from the phase 3 REACH3 trial for steroid-refractory chronic graft-vs-host disease.
Matt Fowler: Now, let’s transition over to the third segment, focusing on the REACH3 trial on ruxolitinib [Jakafi]. Could you talk about the study inclusion criteria for patients to enroll in this phase 3 trial?
Yi-Bin Chen, MD: The REACH3 was a phase 3 randomized prospective clinical trial involving patients with steroid-refractory chronic graft-vs-host disease. Patients were 12 years or older. They had moderate to severe steroid-refractory or [steroid-]dependent chronic graft-vs-host disease and obviously gave informed consent to be randomized to either ruxolitinib or a control arm that was called best available therapy, or BAT. All credit to the investigators as well as Incyte [pharmaceutical company] for conducting this landmark trial in steroid-refractory chronic graft-vs-host disease. We just haven’t had a lot of large phase 3 randomized trials in the field of transplant at all, and certainly in graft-vs-host disease. This effort really goes to show that we as a community can, and should, conduct these trials. The control arm is not perfect because there is no consensus on what should be standard second-line therapy for chronic graft-vs-host disease and being this was an international trial, there were obvious differences in care depending on the region, the center, the provider, and so forth. REACH3 did its best by giving a bunch of options for best available therapy and that was as good a control arm as possible. The population was who we see: moderate to severe patients, ages 12 and older with steroid-refractory or steroid-dependent chronic graft-vs-host disease.
Matt Fowler: You mentioned the best available therapy arm. Could you go into a little bit more detail of what the treatments were that were included in that arm?
Yi-Bin Chen, MD: The options for best available therapy on the REACH3 trial that were specified included photophoresis or ECP [extracorporeal photopheresis]; low dose methotrexate; mycophenolate mofetil; mTOR [mammalian target of rapamycin] inhibitors, such as sirolimus [Rapamune] or everolimus [Afinitor]; TNF [tumor necrosis factor] inhibitors, such as infliximab [Remicade], rituximab [Rituxan], pentostatin [Nipent], and imatinib [Gleevec]. Then, halfway through conducting the trial, ibrutinib [Imbruvica] was approved as I mentioned before, and so an amendment was added to allow patients to receive ibrutinib as part of best available therapy as well, but those were the options for best available therapies.
Matt Fowler: Looking at the study itself, what were the primary and key secondary end points, and really how were they measured overall?
Yi-Bin Chen, MD: The primary end point of REACH3 was overall response rate by NIH [National Institutes of Health] criteria at 24 weeks after randomization. Then the key secondary end points included failure-free survival as well as the difference in adverse events. Then, even more important perhaps, as is becoming more popular from trials of chronic graft-vs-host disease, was a patient-reported outcome called a modified Lee Symptom Scale. Because chronic graft-vs-host disease is a disease that usually does not rapidly cause mortality and because the judgment of its response is difficult using the NIH consensus criteria, which is the best we have, there is a huge range of partial responses, from partial responses that may be life-changing and significantly matter to those where a patient can’t even tell a difference at all. The best way to try and quantify that or prove that responses matter is, at this point, through patient-reported outcomes, or PROs. The best we have for patients with chronic graft-vs-host disease would be a tool such as a modified Lee Symptom Scale.
Transcript Edited for Clarity