Steroids for First-Line Treatment of Chronic GVHD


Yi-Bin Chen, MD, leads a discussion on the use of steroids as first-line treatment of chronic GVHD and when to switch therapy.

Yi-Bin Chen, MD: We’re now going to discuss strategies to treat chronic graft-vs-host disease [GVHD]. As much as we’ve all been excited about the advances in the treatment and prevention of acute graft-vs-host disease, there’s been a lot of progress in chronic graft-vs-host disease as well. Unfortunately, when we see patients with chronic graft-vs-host disease in the clinic, we still treat patients with steroids first-line, just like in acute. We treat patients with systemic prednisone at a dose between .5 to 1 mg/kg per day. That treatment strategy hasn’t changed in a couple of decades.

Some of these patients have been through a lot in terms of complications. Some of them have been on steroids in the past for acute graft-vs-host disease, and adding steroids again at that juncture often creates a lot of morbidity. That has been well documented in the past. It can be anything from infections to bone health, hypertension, mood swings, and so forth. All of us feel there has to be some improvement on that. Better yet, if we were able to predict how patients would do with steroids or have a glimpse into the biology, we could change it. Sophie, do you want to talk about how we think we could better monitor patients on steroids for chronic graft-vs-host disease?

Sophie Paczesny, MD, PhD: One is the availability of samples. We need to do the same approach as we have done for acute GVHD to get the response to treatment and get the samples after you started a treatment. I tried these for biomarkers. It will be nice to have a biomarker at the beginning of the treatment and then also follow the biomarker to see their predictability, as well as the monitoring after treatment. There aren’t that many samples available in academia that are taken at onset of the treatment. This is a gap that should be filled. But if you have these samples, I don’t think it’s difficult to find a new biomarker in this. I know that the company has tried to get on their phase 3 trial with samples. It’s a question of seeing the biomarker for this. I believe they’re collaborating with MAGIC [Mount Sinai Acute GVHD International Consortium], and they may have also their own biomarkers. We’ll see what comes out of this.

Yi-Bin Chen, MD: Current clinical trials are a great opportunity because they’re well organized. If we have the samples, we should commit them to discovery for this type of research. Nelson, when you’re in the clinic and see a patient with chronic graft-vs-host disease on steroids, when do you know to add something else? When do you know it’s not working for chronic graft-vs-host disease?

Nelson J. Chao, MD, MBA: Usually, the patient will tell you. It’s chronic, so they have this for a while, and they’re probably the best markers. They will tell you when they’re not feeling well. Sometimes the clinical findings aren’t that impressive because quality of life and their performance status is a key component. Usually, if you’re measuring skin thickness or you’re doing the NIH [National Institutes of Health] consensus criteria measurements, you can look and document that grade by grade in each of these organs. But in general, the patients let you know.

Hannah Choe, MD: That’s more frequently captured now with the modified Lee Symptom Scale, too. Now we’re able to pose that to the patient in a more uniform manner that’s evidence-based to determine earlier symptoms as well. To your point, because it’s chronic, it’s much slower than acute. The progression of worsening symptoms happens slowly, as well as the response. When we start a new treatment, we can’t wait 6 days like we do with acute; we wait 6 weeks. Unfortunately, there’s a high rate of corticosteroid refractoriness in all of our patients; about 50% are corticosteroid-refractory. When we start a therapy, there’s the initiation of therapy, hopefully response within 6 weeks, then monitoring for 6 months. The switch to tapering steroids or to another line of therapy is much more drawn out compared with acute.

Yi-Bin Chen, MD: These are all important points; that it’s not just looking at the organ grading, but comprehensively talking to the patient about how they’re doing. That’s why in the trials that have gotten agents approved, they include patient-reported outcomes, such as quality of life. We know how important that is for chronic graft-vs-host disease.

Transcript Edited for Clarity

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