Frontline Treatment Options for Chronic GVHD
The panel reviews treatment approaches for graft-versus-host disease when steroids are not an option and explains how the heterogeneity of GVHD makes finding the right treatment challenging.
Nelson Chao, MD, MBA: Here's a patient who we restarted steroids and responded. Do you restart the prophylaxis regimen if they were on a calcineurin inhibitor, for example, or do you use steroids alone? Start with Hana.
Hana Safah, MD: I usually don't. Studies have shown that adding again for chronic GvHD with steroids, calcineurin inhibitors, or other immunosuppressants usually doesn't offer significant benefit. There was a study that showed maybe adding cyclosporine can, for steroid-sparing purposes, maybe shorten the duration. But not significantly. So, as a routine, no. I start steroids and I do steroids alone. Is there a patient that I have used a combination for? There is no hundred percent in medicine. So, yes, maybe here and there. The patients that I might consider are those who have not received Prograf for a long time, for instance, because they didn't have any evidence of GvHD and I was able to taper it within sixty days from stem cell transplant or less. I might add it until I get something else to be added later if I want to shorten the duration of the steroid. But in general, I do not.
Catherine Lee, MD, MS: I have done it both ways and I have seen my colleagues do it both ways. Typically, what we do at the Hutch is, if we find that GvHD develops while someone is on a tacrolimus taper, for example, and their level is at three, and they start to develop GvHD warranting corticosteroids, we would increase the tacrolimus dose to get up to the therapeutic level again and also begin corticosteroids. If the patients have been weaned off their immunosuppression and they've been off for two weeks or maybe four weeks and then chronic GvHD begins, I think many of us would feel comfortable just treating with single-agent corticosteroids.
Nelson Chao, MD, MBA: What about if you can't use steroids? They had steroid psychosis and they're just scared. Is there something else we can use for this patient?
Catherine Lee, MD, MS: When I had a clinical trial that used a non-steroid agent in the frontline setting in combination, we would obviously put this patient on the clinical trial. I think that's a challenging situation that you mention. It depends on how the patient is presenting, with what organ involvement, and how severe their symptoms are. That is a difficult question. I might try to re-challenge them with steroids and support them. If they have steroid psychosis, I may work with my psychiatry colleagues and try to develop a plan that might help control the psychosis. Outside of a clinical trial, I have not yet used ruxolitinib or another agent as frontline therapy in this type of situation.
Hana Safah, MD: Are you asking about the use of sirolimus as a single agent in such a patient?
Nelson Chao, MD, MBA: Yes. I would do exactly what Catherine says. I would go for a clinical trial first.
Hana Safah, MD: Yes, definitely. Catherine is right.
Nelson Chao, MD, MBA: There are data to suggest that perhaps in a low-risk patient, sirolimus could be used. To be honest with you, I have not done it very often because I still think steroids are the choice. But there are a lot of problems with steroids, I would say. I think we all know that. It's not the easiest drug to use.
Hana Safah, MD: Very true. With skin, I would do sirolimus if they have psychosis as a first-line treatment and then start them on ECP. I believe ECP can do a good job with skin GvHD, but it takes time, and it takes a long time. And then you have to have invasive line placement, a central line for the procedure itself. I think you were asking about sirolimus, and I would use it except I don't know. Does it work in your experience when you have superficial sclerosis? I see it working well with hyperpigmentation, but when it comes to sclerosis, does it work in your experience?
Nelson Chao, MD, MBA: I would probably reach for ECP earlier rather than later. We tend to use ECP. I don't know, does Hutch or City of Hope use ECP?
Catherine Lee, MD, MS: Yes, we offer ECP. I will say most patients are not enthusiastic about traveling to the center to use that.
Erin Kopp, NP: I think it was interesting that we all took a pause as soon as steroids are off the table. I think that's such a critical thing to acknowledge because steroids are the mainstay. It's our consensus; it's the one thing we know. And in the chronic setting, "chronic" may be a misnomer when we're talking about what's in front of our face. It's chronic in terms of the etiology. It's chronic, perhaps, in terms of what we're going to see, but if I had a patient—like you said—if I had a patient who had superficial sclerotic changes versus a patient who had significant GI or liver issues that I needed to address in the next week, I think that also changes our approach in what we're comfortable giving. Right? For skin alone, ECP, of course, and if there wasn't a clinical trial. But outside of that, corticosteroids are the space that we use when we need it fixed now. Because I think the majority of our second-line agents that are available have differing times to action, and so that's one thing. And the heterogeneity of chronic GvHD is also the major driver, I believe, in why it's so difficult to come to a consensus about each patient. Two patients with the same "moderate" chronic GvHD, seeming to present in the same fashion, will respond differently to treatment and have a different level of urgency based on how quickly we need to see that change. I could almost feel a visceral response from all of us when you said steroids are gone because it's really a challenge. Especially when we are so accustomed to what we do in acute cases, and we see that response, and then we know that the patient is improving, and we feel better, and they feel better.
Catherine Lee, MD, MS: I had a patient—luckily, I had my clinical trial available—but if I hadn't had it available, she could not tolerate steroids. I was actually thinking of bringing her inpatient and desensitizing her to prednisone to see if that could work. I completely agree with you. It's relatively not a common situation, thank goodness, but it's a very challenging situation.
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