The Ongoing Fight Against Acute GvHD - Episode 6

Practical Advice: GVHD Management With REACH2 Regimen

November 6, 2020
John DiPersio, MD, PhD

John F. DiPersio, MD, PhD: We still need to learn a lot about how to give this drug. The major problem is that many patients who get it will get some level of anemia and thrombocytopenia. But you never know whether this is because of the GVHD or the drug. The addition of azoles, especially strong CYP3A inhibitors, might actually increase that level of toxicity because of drug metabolism issues.

We still don’t know exactly how to manage these patients in the context of modern azole therapy for antifungal prophylaxis, No. 1. But I usually start at 10 mg by mouth twice a day in patients who have severe acute GVHD [graft-vs-host disease]. For patients who have flares of GVHD, if I want to give them a JAK inhibitor to reduce the long-term exposure to steroids, I’ll usually start at a lower dose, 5 mg twice a day, and see how their blood counts tolerate it.

For patients who have true steroid-refractory acute GVHD, these are patients who have a high likelihood of dying over the next month or 2. So you need to get control of the disease immediately. If too much tissue damage occurs in the GI [gastrointestinal] tract, it may take the GI tract months and months to recover, even if you stop the process. So these patients die frequently of infections and things.

My recommendation is to use JAK inhibitors as the primary intervention for patients with steroid-refractory acute graft-vs-host disease based on this study and based on the itacitinib trial, because it’s a similar class of drugs, and also the preclinical modeling in the mouse. We think it’s an effective drug.

The dose of JAK inhibitors is up in the air. Obviously, the recommended dose in these patients is 10 mg twice a day. But for patients who have marginal blood counts and have a flare, and you want to try to reduce their exposure to steroids, starting at a lower dose and escalating to a higher dose might be a reasonable approach, especially if they’re on a strong CYP3A inhibitor, such as some of the azoles.

Transcript edited for clarity.