The Expanding Field of GVHD - Episode 12

Steroid-Refractory Chronic GVHD: Selecting and Sequencing Therapy

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Following their review of available treatment for steroid refractory chronic GVHD, experts consider how they would optimally select and sequence therapy.


Corey Cutler, MD, MPH, FRCPC: We’ve alluded to this, but we have 3 drugs in front of us. We have the opportunity to choose, at some level, which drugs we want to use. Briefly, the way I approach this, staying on-label, is for patients who have underlying B-cell malignancies, I’ll often choose ibrutinib as an immunosuppressive for second line or beyond in chronic GVHD [graft-vs-host disease], thinking that it might provide some element of protection against disease relapse. But for the most part, I’ll choose ruxolitinib first, followed by belumosudil. For subjects with lung disease, I’ll try to find a way to get belumosudil into them earlier, but it’s difficult because it’s only indicated in the third line. Linda, Yi-Bin, why don’t you tell us how you sequence these drugs.

Yi-Bin Chen, MD: Linda, do you want to go first?

Linda Perry, PA-C: I agree with you, Dr Cutler. We typically go to ruxolitinib first and then turn to belumosudil. We definitely have had some favorable responses with the lung GVHD and belumosudil. But the indication is after 2 or more lines of therapy, so it’s hard to get to. With respect to the ibrutinib, there are select patients who we’ll turn to for ibrutinib, similar to what you’ve said with the underlying B-cell malignancy. But typically, we’ll sequence ruxolitinib and then try to get belumosudil.

Yi-Bin Chen, MD: Our practice doesn’t differ much. That’s our sequence as well. I’d also agree with the underlying B-cell malignancy comment, with the caveat that that’s a shrinking population for our allotransplant offerings. After the use of ruxolitinib, we do generally have a conversation about ECP [extracorporeal photopheresis], depending on the manifestation. Certainly, for skin or sclerodermatous disease, we’ve had a good experience with photopheresis. It’s just that ECP involves a big investment of resources from the patient in terms of trips back to the center, as well as possibly an indwelling catheter and so forth. ECP has a role, but oftentimes the logistics get in the way of easily using it.

Corey Cutler, MD, MPH, FRCPC: ECP is 1 of a number of things that can be used in this scenario. Some of us still use B-cell–depleting therapy like rituximab, particularly in patients who haven’t had a trial of ibrutinib, so I wouldn’t use it in ibrutinib-resistant patients. There are a couple of other things that we can pull out of our bag of tricks. The mTOR inhibitor sirolimus was 1 of the first drugs to be proven to have activity in chronic GVHD. I’ve taken to using low-dose weekly oral methotrexate, particularly in patients who have psoriasiform-like chronic GVHD and even ocular GVHD; it can be fairly effective there. It’s important that we don’t turn our backs on some of the agents we’ve used in the past. In rare scenarios it can be quite effective and nontoxic.

Transcript edited for clarity.