Considerations for novel treatment approaches with approved agents in combination or the frontline setting of chronic graft-vs-host disease.
Corey Cutler, MD, MPH, FRCPC: The future of management of steroid-refractory chronic GVHD [graft-vs-host disease] is to better understand which drug is right for the individual patient. It’s also understanding rational combinatorial therapy and selectively combining 2 or more of these agents in patients, and whether we should be using these drugs outside their labeled indications, such as in first line, which depends on the results of clinical trials. I try not to prescribe these drugs in the first line because of our clinical trial experience. We have a clinical trial that evaluated ibrutinib in combination with corticosteroids as frontline therapy for chronic GVHD. Unfortunately, that trial didn’t demonstrate a benefit for the combination of the 2 drugs in frontline therapy. The reasons for that are variable, and we can discuss that. However, the fact that we have randomized data suggests that we should be following that data. I’m looking forward to the clinical trials that evaluate drugs such as ruxolitinib or belumosudil in the frontline setting, but for now, I’m not using them in that setting outside a clinical trial.
Yi-Bin Chen, MD: We don’t know how to use these drugs in sequence or in combination. I don’t think we know how to stop these drugs either. Meaning, do we stop them cold, or do we have to taper them? We need some real-world studies that show the safety and efficacy of combining these agents. In my practice, I don’t use a lot of ibrutinib. Ruxolitinib is our standard second-line agent. With the access to belumosudil, which started in fall 2021, we’ve written a handful of prescriptions for patients who are already on ruxolitinib. I have several patients on both, and theoretically it didn’t seem like it would be harmful. That’s borne out: it appears to be safe, but we need a larger cohort of patients on both agents to show the safety. Part of the reason is that in not everyone to whom I’m adding a third-line therapy do I determine the second-line therapy hasn’t worked at all. If ruxolitinib hasn’t worked at all, I’ll stop it and add the third-line therapy. But if I feel patients achieved partial response, but it wasn’t good enough for the quality of life and I felt like we wanted to do better, then I don’t feel that I could stop the ruxolitinib because it helped. Those are the patients who have been on combination therapy. I haven’t started multiple agents at once. I’m not sure I believe in that approach. We haven’t seen data there, but we look forward to more of that experience from our practice and others.
Haris Ali, MD: Chronic GvHD is a debilitating illness in patients who either have it or would like to prevent it. Before it happens, a lot of new treatments are looking into prevention of chronic GVHD. It would be the early detection, and some of the novel agents that can decrease the fibrosis that can happen in late stages would be the unmet need.
Transcript edited for clarity.