Yi-Bin Chen, MD: In 2019, ruxolitinib became the first agent ever approved by the FDA for the treatment of acute graft-vs-host disease. It was approved for patients 12 years and older to treat steroid-refractory acute graft-vs-host disease. This was based on a pivotal trial called REACH-1, which was published by Madan Jagasia and colleagues in 2019. This was a single-arm phase 2 trial of 71 patients with steroid-refractory acute graft-vs-host disease who were treated with ruxolitinib. They were treated first at a dosage of 5 mg twice a day, and after 3 days if they tolerated such, the dosage was increased to 10 mg twice a day.
The day 28 overall response rate, which has emerged as the pivotal primary end point for such trials, was a compelling 55%. And all patients on study, if you looked at best response, was as high as 73%. The day 28 complete remission rate was 27% and best complete remission rate was all the way up to 56%. Most impressively, the 6-month overall survival was 51% which is a really great number to see for a subset of patients who traditionally had dismal outcomes.
When the FDA looked at those 71 patients in the trial, they determined that only 49 of them qualified for their strict definition of steroid refractory. But even in those 49 patients with strict eligibility for steroid refractory, the day 28 overall response was really impressive, 57%. And these really compelling outcomes laid the groundwork for the approval of ruxolitinib for steroid-refractory acute graft-vs-host disease.
Corey Cutler, MD: REACH2 was a very important clinical trial in our world. This was a very large randomized trial. Over 300 patients were randomized to receive either ruxolitinib or 1 of 9 alternative best-available therapies for the management of steroid-refractory acute graft-vs-host disease. The primary end point was the response at day 28, and in this trial the response in the ruxolitinib-treated patients was 62%, where it was only 39% in the patients receiving best supportive care. Patients also had a higher likelihood of having a durable response by day 56 in the ruxolitinib, so that was 40% versus only 22 in the control arm. And the rate of loss of response down to 6 months was low in the ruxolitinib group, so it was only 10% versus almost 40% in the control group. There was an improvement in median overall survival, and overall this was a very positive trial for us and really establishes ruxolitinib as a very good choice for steroid-refractory acute graft-vs-host disease. This builds on the REACH-1 results, which were very similar, but this in a randomized setting predominantly performed in European centers really adds some credence and some weight to the approval of ruxolitinib based on the REACH-1 data.
In terms of safety, the main signals in the ruxolitinib arm were related to cytopenias, which is what we would expect from this drug, knowing what the adverse-effect profile is. About a third of the patients in the ruxolitinib group had thrombocytopenia, and almost a third had some degree of anemia. There didn’t appear to be much of an infection signal, so these patients who have steroid-resistant acute graft-vs-host disease have a very high incidence of infections. Ruxolitinib did not appear to increase that rate of infections in comparison with the other best supportive care. All those types of therapies are associated with excess infections, except things like extracorporeal phototherapy, which typically is not.
Transcript Edited for Clarity