Advances in the Management of Graft Versus Host Disease - Episode 13

Clinical Manifestations of Chronic GVHD

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Drs Hannah Choe, Nelson J. Chao, Sophie Paczesny, and Yi-Bin Chen share their approach to treating patients with chronic GVHD who present initially with either scleroderma or bronchiolitis obliterans.

Yi-Bin Chen, MD: I want to talk a little about the 2 most difficult manifestations of chronic GVHD. There’s systemic scleroderma, or an imitation of systemic scleroderma. Depending on where in the body it affects your patient, it limits range of motion. If it’s in the torso or the trunk, it may limit breathing and appetite. It’s very disabling, depending on the extent and the location. The other is bronchiolitis obliterans syndrome [BOS], or pulmonary chronic graft-vs-host disease [GVHD]. Let’s touch on scleroderma first. Hannah, let’s say a patient walks in and they have new scleroderma. My reaction is that they’ve had this for a while and either I’ve missed it, they haven’t told me, or I haven’t seen them enough because they’re not coming to the center anymore. Do you treat that patient differently in terms of initial therapy for chronic GVHD?

Hannah Choe, MD: Initially, depending on if they have no other manifestations of chronic GVHD, I would potentially move to ECP [extracorporeal photopheresis] earlier. That’s because we have a lot of experience with having responses in this typically therapy-refractory population. Using ECP with a long duration and a very long commitment, we do see responses. Whereas the responses that we get with other agents are usually very partial and limited. To have a more durable response, I’ve found that ECP is more beneficial. But if they have other manifestations besides scleroderma, then I’d be more inclined to use ruxolitinib or belumosudil in that setting.

Yi-Bin Chen, MD: Do you think steroids work for scleroderma?

Hannah Choe, MD: Not effectively.

Yi-Bin Chen, MD: You’re very pessimistic. It’s almost like a necessary evil and you know you’re going to add something else. Do you have the same feeling?

Nelson J. Chao, MD, MBA: I do. That’s true.

Yi-Bin Chen, MD: I tend to have a very short time before I add on ruxolitinib or talk about ECP—depending on patient logistics—when I see a patient with scleroderma. I feel bad when I start steroids because I already know they’re probably not going to work for that patient, yet it remains a standard of care. My feeling is if there’s some erythema, maybe there’s some active inflammation. But once you see the scleroderma, you already know there’s a permanence to this. It bespeaks to deficits in monitoring and perhaps in patient education. Patients oftentimes don’t want to believe they’re sick at that point, so maybe there’s denial going on as well. Sophie, what do you think about bronchiolitis obliterans? Is there a reason to believe we should treat that differently from other forms of chronic GVHD?

Sophie Paczesny, MD, PhD: It’s the same as scleroderma. The problem is that when you treat and target, there’s immunosuppression and you have a higher risk of infection. BOS isn’t too mild of a pulmonary infection. You have to intervene early. ECP is probably 1 way to go so that you don’t increase the infection risk. The other thing we don’t talk about is that we’re targeting the T cell, which also fights against infection. I prefer something softer, like ECP. For BOS in an organ transplant, ECP is FDA approved because it’s better tolerated. What about you? What do you do for that?

Yi-Bin Chen, MD: We frankly don’t know what the best therapy is. There are local pulmonary topical steroids, inhaled corticosteroids, and so forth. We add systemic steroids for most patients to start, again with this pessimism that it’s probably not going to work. There are ongoing trials that will be interesting to see. We have 1 in our center [Massachusetts General Hospital] using ruxolitinib for patients with newly diagnosed or refractory BOS to study the lung-specific effect. There are investigators looking at the ROCKstar data set to see if they can tease out how well the lungs responded to belumosudil as well to give some inkling of whether this is an effective therapy for the pulmonary manifestation. I’m not optimistic that we’re going to see tremendous improvement in the lungs. A victory might just be stable disease and not getting worse, but I’m not sure. Just like scleroderma, once BOS sets in, I’m not sure how truly reversible it is.

Nelson J. Chao, MD, MBA: Our problem is that we don’t look. If we found it earlier, we might see better responses than what we’re doing. One thing that might be very helpful is that many centers, including ours, are doing outpatient home monitoring. It’s continuous medical monitoring for respiratory symptoms, heartache, temperature, and so forth. It may be that we’ll be able to pick up signs of this much earlier. I’m convinced that we could certainly pick this up before patients come to you saying they’re short of breath. By that point, it’s pretty late.

Yi-Bin Chen, MD: Absolutely.

Sophie Paczesny, MD, PhD: There are some clinical trials that look at the peak flow regularly. Monitoring is also key, along with supportive care for avoiding infection when you start the new treatment and probably also this new agent. ROCK2 inhibition and CSF1R will probably help for something more macrophage related, like BOS or scleroderma.

Yi-Bin Chen, MD: Right.

Transcript Edited for Clarity