Graft versus Host Disease Practice Updates - Episode 9

Scenario 2: Selecting Therapy for Steroid-Refractory GVHD

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Having reviewed approved treatment options for steroid-refractory, chronic GVHD, experts discuss how they would address this patient scenario.

Transcript:

Nelson Chao, MD: Going over the data in the guidelines, what treatment would you select for this patient at this time? Dr Cutler?

Corey Cutler, MD, MPH, FRCPC: Going back to the case, this is someone who did have a response to corticosteroids when they had myofascial-type symptoms but now has a real sclerodermatous disease. It would be tricky to call this failure of 2 or more lines of therapy. I’d like to use belumosudil because of the antifibrotic properties that drug has, but from a regulatory point of view, ruxolitinib would probably be my choice. The reasons why I’d choose ruxolitinib over ibrutinib in this scenario is that this patient wouldn’t qualify for the ibrutinib trial as it was designed. In that initial 42-person study, patients had to have the inflammatory manifestations of chronic GVHD [graft-vs-host disease], such as an erythematous mouth or an erythematous skin rash, and this patient has neither of those. So I’d choose ruxolitinib or belumosudil at this point. Of course, if there were a clinical trial available, that would be my first choice, particularly if a trial of axatilimab, for example, was available. There are other options to use here. But staying within the approved agents list, I’d switch to ruxolitinib or belumosudil if I could get it.

Nelson Chao, MD: Dr Minor, what are some of the adverse events that you see in these patients that would guide you 1 way or the other?

Kerry King Minor, MSN, ANP-BC: One thing I always take into consideration is what they’ve tolerated in the past. I don’t want to leave people on corticosteroids for long periods of time, but some people do OK. Many have glucose levels over 300 mg/dL, and they just melt in front of you. Knowing about a patient and how they responded is important. Similarly, before we had some of these other steroid-sparing agents, we were just slapping things on them, and we might go back to a calcineurin inhibitor. If I knew someone’s blood pressure shot through the roof or they had kidney issues at this point, that would impact whether I’d be able to use that agent again. But now the thought is, we some other agents that we can stun them with, initially with corticosteroids, and then put them on a steroid-sparing agent, which will get them off the steroids much faster. In doing that, you can hopefully avoid some of these adverse events that they may have seen in the past when the previous players of GVHD had presented themselves.

Nelson Chao, MD: I think that’s true. It’s encouraging that we’re moving to a phase where we have a more standardized approach to treat these patients after steroids because it’s been so center-specific and boutique-like that it’s been difficult to compare data. One of the better things we’ve done with the BMT CTN [Blood and Marrow Transplant Clinical Trials Network], as well as some of these larger pharma studies, is recruit patients to answer some of these important questions. From what I’ve been hearing, the nice thing about belumosudil is that it’s well-tolerated, and there were very good responses. Ruxolitinib works. The tolerability is a little more difficult because of the known toxicities to the marrow. Some patients don’t have great counts. One problem with chronic GVHD has been the impact on the marrow. Sometimes they end up with very low platelet count studies. And it may be very difficult to use some of these drugs because of the heme toxicity.

Transcript edited for clarity.