JAK Inhibitors: Managing Cytopenias in Chronic GVHD

EP: 1.Overview of Graft vs Host Disease (GVHD)

EP: 2.Role of Early Intervention in GVHD Treatment

EP: 3.Risk Factors for GVHD

EP: 4.Frontline Management of GVHD

EP: 5.Approaching Initial Treatment of Chronic GVHD

EP: 6.Third-Line Treatment Approaches for Acute GVHD

EP: 7.Management of Chronic GvHD

EP: 8.Challenges in Managing Chronic GvHD

Now Viewing

EP: 9.JAK Inhibitors: Managing Cytopenias in Chronic GVHD

EP: 10.Practical Considerations for the Treatment of GVHD

EP: 11.Role of Ruxolitinib in GVHD Treatment

John DiPersio, MD, PhD: There may be a certain degree of precision medicine that is escaping us here. Obviously, you and I have seen these, I’ve seen some patients with bad chronic GVHD [graft-vs-host disease] who have enormously impressive turnarounds with photopheresis, not many unfortunately. The question is for those patients in particular, what’s the biology of their disease? Why do they seem to respond so much better than the other 80% or 90% of patients who get photopheresis and at best, their disease sort of holds stable?

Michael Bishop, MD: Do you think it is those patients whose T-regulatory cells [T-regs] do improve?

John DiPersio, MD, PhD: It could be, yes.

Michael Bishop, MD: That’s about the only thing, nobody understands why, but we do see that in the responding patients that T-regs seem to improve.

John DiPersio, MD, PhD: Yes. We’ll see what happens with chronic GVHD, but the Holy Grail going forward is again, it’s when you get it and it’s bad, it’s bad…. The other thing, Mike, is that for all of these treatments, if you look at all of them as far as pulmonary responses, which is the most dreaded complication of chronic GVHD, progressive diminution of vital capacity and pulmonary function. If you look at all of them, Syndax [axatilimab], the ROCK inhibitor, Jakafi [ruxolitinib], photopheresis, the one area that doesn’t seem to improve even though you can improve the skin and muscle, and flexibility, and eyes and mouth, is the lungs. If you look at all these studies, the improvement in the lung disease has been negligible.

Michael Bishop, MD: Yes. It’s always when they list the organs in terms of response, it’s always the last, and liver comes in a close second, but particularly in lungs because it’s so devastating clinically in what it does to patients’ quality of life. I agree with you, the biology there to understand why, as you were talking about before, it comes back to B- and T-cell biology, this endothelial damage and what we think is deposition of aberrant monoclonal antibodies. It is disappointing. And again, it comes back probably to your primary theme of treat early and treat aggressively before you see these significant changes occur because it can provide some stability. If I had stability in those patients with bronchiolitis obliterans, I would be happy on a relative scale.

John DiPersio, MD, PhD: Now, I wanted to ask you, what’s your policy and sort of your own institutional guidelines for when patients do have chronic GVHD and they’re on a JAK inhibitor, for instance, how long do you continue the treatment, indefinitely, or do you treat for 6 months, and then if there’s no further improvement, do you stop?

Michael Bishop, MD: We would stop if there’s no improvement, but if we get close to complete response, we will try to taper. Personally, I don’t go from 10 to 5 mg, I’ll do instead of 10 mg BID [twice a day], I might go to 10 and 5 mg, and then 5 and 5 mg, rather than just jumping down. Whether that’s correct or not, I don’t know, but I’d rather do it like a steroid taper. I just don’t want that block off, and that might biologically, maybe it’s already inhibited enough. But I tend to try to taper, so if they’ve had an outstanding response, I try to taper off, but I make sure they’re off steroids first. We tend to keep ruxolitinib on for a long time as long as they’re tolerating it. In my experience, the cytopenias are quite manageable. I’ve had very few patients where I’ve had to stop because of adverse events.

John DiPersio, MD, PhD: Yes, I wanted to make that point. This was the reason why these things were never studied up front even though our laboratory had pushed this from the very beginning. No one wanted to do it because of this potential risk of cytopenias. In our mouse models, we showed that these drugs improved hematopoietic recovery, they didn’t decrease it. And then it probably has to do with the fact that they reduced GVHD.

Michael Bishop, MD: Right, and the negative effects, exactly right, on the bone marrow.

John DiPersio, MD, PhD: The cytopenias we see when we put people on JAK inhibitors, we automatically attribute it to the drug, but we see them also in patients who aren’t being treated as a component of, especially acute GVHD.

Transcript Edited for Clarity