The Changing Landscape of Chronic Graft vs. Host Disease - Episode 10

Practical Considerations for the Treatment of GVHD

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Expert hematologist/oncologists consider combination therapy with ROCK and JAK inhibitors for the treatment of chronic GVHD as well as the use of ibrutinib for disease management.

John DiPersio, MD, PhD: Let me ask you also about, I don’t know if you’ve had the same length of experience, either in trials or after the ROCK inhibitor has been approved. When you have a patient on a JAK inhibitor, ruxolitinib, for chronic GVHD [graft-vs-host disease], and you get to a point where they’re not improving much more and they’re still complaining and not getting much better, you just told me that you tend to, unless they really decline, you probably keep them on if they’re stable. But what about adding a ROCK inhibitor, would you stop the JAK inhibitor, or would you add them both together?

Michael Bishop, MD: Well, you know, that’s a good question. We have added on agents. I don’t have that large of an experience with ROCK inhibitors where I can say that. I’d be interested to hear what your experience is, but we have added on agents, as I mentioned before, with the hope that we’re still getting some benefit, but we need something extra. If we clearly see there’s zero response, we’re likely to stop the ruxolitinib. We have occasionally switched to ibrutinib. Whether that play makes any sense, you could argue. But again, as you know, when you’re getting to third- and fourth-line treatments for chronic graft-vs-host disease, you reach to whatever life preserver is there.

John DiPersio, MD, PhD: I would say, nobody’s had that much time with both drugs. We’ve obviously given JAK inhibitors, ruxolitinib, to many patients, and now we’re tending to add on a ROCK inhibitor to it and not discontinuing it because we have the same concerns that if you just stop it, there will be some patients who may flare. And they work through completely different mechanisms, and they work largely maybe even through different cells. ROCK inhibitors certainly have anti–T-cell function, but they also have inhibitory functions on monocytes and macrophages, and neutrophil enzyme and proteases, and things like that. We tend to add them together, and we’re going to see if the 2 together actually have benefit.

Michael Bishop, MD: Just from a management standpoint, drug-drug interactions, what do your pharmacists say?

John DiPersio, MD, PhD: So far, they have said that there are no obvious drug-drug interactions, so we’ve not been dosing them differently. The ROCK inhibitors get dosed based on whether they’re on azoles or a proton pump inhibitor.

Michael Bishop, MD: Right.

John DiPersio, MD, PhD: What about ibrutinib? Where do you put that in your armamentarium for chronic GVHD; are you skipping by it, are you using it? If people progress on JAK inhibitors, do they go to photopheresis or do they go on ibrutinib?

Michael Bishop, MD: We so use a fair amount of ibrutinib. That would be next line for us. We do believe in, that’s probably a poor choice of words, but ECP [extracorporeal photopheresis] becomes our third line. But then we will think about the use of ibrutinib, and we do use a fair amount of ibrutinib in our chronic graft-vs-host disease, particularly if they have not had any significant response to ruxolitinib.

The only thing I caution about is that these patients have thrombocytopenia often with chronic graft-vs- host disease. A lot of my older patients already have cardiac problems. Some of the second-generation BTKs [Bruton tyrosine kinase inhibitors], some people are looking at acalabrutinib. I would be more comfortable if that had been well studied in chronic graft-vs-host disease because I feel more comfortable with it relative to potential adverse effects. I do think that’s part of the decision-making process of how I’m going to treat a patient, I am looking at those potential adverse effects and coming back again to quality of life. That was my hesitancy when you asked me about ibrutinib.

John DiPersio, MD, PhD: Yes. We’ve used, again like you, a fair amount of it, but I would say that it’s not nearly as commonly used as any of the other things we’ve been talking about.

Michael Bishop, MD: They are our third- or fourth-line agent, depending upon the patient and their situation.

John DiPersio, MD, PhD: Exactly, and we’ll certainly go to clinical trials even before we put someone on ibrutinib, meaning that we aren’t as confident with the results, a small single-arm study. Although the results seem compelling, in the real world, our experience has not been as compelling. That’s been the hold up, and appropriately so. If the trials were done like the REACH3 study was done, I think we’d probably have more confidence and probably use it more frequently. It does have some unfortunate adverse effects from time to time in patients as well.

Transcript Edited for Clarity