Stephanie Lee, MD, MPH, discusses the study of ruxolitinib plus best available therapy as a second-line treatment for patients with chronic graft-versus-host disease.
Stephanie Lee, MD, MPH, a hematologist and blood and marrow transplant physician-scientist and a professor and associate director of the Clinical Research Division at the Fred Hutchinson Cancer Research Center, discusses the study of ruxolitinib (Jakafi) as a second-line treatment for patients with chronic graft-versus-host disease (cGVHD).
Systemic glucocorticoids are a key component of front-line therapy for patients with cGVHD, according to Lee’s research, but 50% of patients become steroid-refractory or dependent. This leaves a need for an effective second-line option for patients with cGVHD. Considering patients have already benefitted from ruxolitinib in the frontline setting, the combination of ruxolitinib and best available therapy (BAT) was explored in the glucocorticoid-refractory population in REACH3 (NCT03112603). Lee completed a subanalysis of the primary end point (objective response rate) to see if ruxolitinib performed better than BAT.
The study was positive for the primary end point, as well as for improvement in failure-free survival, and greater symptom improvement. The safety profile of ruxolitinib was also consistent with prior reports.
0:07 | So, I think standard of care for initial therapy is pretty straightforward. You know, most people would agree at this point of time, it's still steroids. Beyond first-line therapy, though, then then it gets murky. Ibrutinib [Imburvica] is currently approved for people who have had at least 1 prior line of therapy. But, there's a lot of people who cannot receive that drug. So, many different agents have been tested.
0:37 | Well, this is based on a lot of other data. So, there's obviously preclinical data that suggests it might be helpful in chronic graft versus host disease. And then there's even clinical data. Ruxolitinib is approved for steroid-refractory acute graft versus host disease. And we're studying chronic graft versus host disease, but some of the mechanisms may be similar. And in addition, there are other reports suggesting that it might be helpful. But those reports were not randomized clinical trials like the 1 I’ll be reporting.
1:11 | I think this was a very well-designed study, which took into account the heterogeneity of practice, really around the world because this was a multinational study. So, it was for patients who had moderate to severe chronic graft versus host disease, who had already had first-line therapy. So, this was the second-line therapy, and that participants were randomized, 1 to 1 to either receive the ruxolitinib starting at a standard dose, which was 10 milligrams twice a day, versus best available therapy. I think a lot of thought went into the study design. We know that there's many different practices around the world and within the United Statesm, and this was really a nod to the idea that we really don't know what is the best second-line therapy. So, there were 10 different agents that the investigators could choose from, and they pre specified which agent they would use for the best available therapy. Then they were randomized to either receive that best available therapy or ruxolitinib. Crossover was not allowed until 6 months, which is when the primary end point was so it was a fairly clean study. I think this is, you know, very generalizable to how we are taking care of chronic GVHD. So, I want to acknowledge that the study really did try to balance, you know, controlling and rigor and everything, and they did a good job of that, but also acknowledge the heterogeneity of practice.
2:37 | So, I mean, the primary results have been already presented by Robert Zeiser at ASH 2020. But I'll be reviewing the primary end point, which was the overall response rate, which was superior in the ruxolitinib arm compared to the best available therapy arm. I’ll also be going over the secondary at the key secondary end point, which was the failure-free survival. So that's the time until you have to start a new agent or relapse or death. Then, the other key secondary end point was the patient-reported outcomes, and this trial was positive for all of those end points. Ruxolitinib was superior to best available therapy.
3:17 | I think a lot of people were already using ruxolitinib now based on the data that we had available. I think this just shows in a much more rigorous trial, that it is, you know, very effective in this indication for second-line therapy. So, this is a registration trial, and they will be putting it forth for FDA approval, and if approved, it would be the second drug that would be approved for chronic graft versus host disease.