Shifting Paradigm in Treating Acute Graft-vs-Host Disease



Corey S. Cutler, MD, MPH, FRCPC: Despite this progress and research, unfortunately we still get acute graft-vs-host disease [GVHD]. What’s the initial approach to GVHD therapy [at Massachusetts General Hospital], Dr Chen?

Yi-Bin Chen, MD: We believe the initial therapy for acute graft-vs-host disease is not where it should be, and there is definitely room for improvement. We believe in trying to conduct clinical trials in the treatment of acute graft-vs-host disease, and to do that appropriately involves a multidisciplinary team of providers and the research staff. Early recognition of graft-vs-host disease is how we are able to see if patients are eligible and present them with appropriate studies to see if they’d like to participate.

At Mass General, when patients present with acute graft-vs-host disease, there is a team of people who are made aware through group emails and oftentimes even before the patient shows up in our clinic, because they’ve called in with symptoms of diarrhea or a rash. By the time the patients have arrived, most of our team—including our research team—is aware that there is a potential patient with new acute graft-vs-host disease, and we’ve already had conversations about what we believe it is and what trials they might be eligible for to participate in.

The patient is to be evaluated to make sure there is a suspicion of graft-vs-host disease. They are presented with the treatment options, including potential enrollment onto a clinical trial. A lot of our clinical trials are biomarker based for risk stratification, and it’s important to get early blood samples to get the results of these biomarkers to appropriately risk stratify our patients.

Corey S. Cutler, MD, MPH, FRCPC: Dr Antin, do you want to talk about the actual therapy? What’s the standard of care for the management of moderate to severe acute graft-vs-host disease?

Joseph H. Antin, MD: It is a little bit of an embarrassment to the field because it’s prednisone or methylprednisolone intravenously, 1 or 2 mg/kg per day until you get it under control. There’s no question that this is an effective treatment. If prednisone were a new drug that were just coming out on the market today, we would be jumping up and down at what a wonderful drug it is because it’s so effective.

The problem with prednisone is that it’s a blunderbuss of therapies. It is not very selective. It does suppress the immune response in an adequate fashion in most patients, but it’s associated with the usual prednisone-related toxicity, hyperglycemia, hypertension, bone mineralization, Cushing syndrome, and sleeplessness. It’s something we depend on and that we use, but we have a love-hate relationship. We love its efficacy, but we hate its toxicity. The most critical aspect is that it increases susceptibility to infection because it’s nonspecific.

Therefore, we have over the past 5-plus years been trying to change the paradigm from a global immunosuppression to either a targeted immunosuppression or a strategy that is not actually immunosuppressive but is more anti-inflammatory. This fosters regulatory T cells, which reduces the target manifestations in the organs. Concomitantly it allows the immune system to recover so that we’re not in the situation where the patient has GVHD, so you hit them with a huge dose of prednisone and you get the GVHD under control. Their disease is under control, but then they die of aspergillosis. That’s much of what we do, and it’s been only in the past decade or so that we’ve started to try to be more surgical in our approach to preventing and treating this disease.

Transcript Edited for Clarity

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