Ruxolitinib for Steroid-Refractory GVHD: The REACH Trials - Episode 3

Initial Management of GVHD

An expert in bone marrow transplantation outlines the main therapy used in the front-line setting to treat GVHD and then provides several definitions of what it means to be steroid-refractory.

Yi-Bin Chen, MD: Now, initial treatment for graft versus host disease, unfortunately, remains high-dose systemic steroids. We'll talk about acute first. In general, if we have to treat acute graft versus host disease, we would give 1 to 2 milligrams per kilograms per day of prednisone or its intravenous equivalent, depending on the patient's clinical manifestations. Traditionally, if it's skin only, we've leaned towards just using 1 mg per kg, and if it involves a lower GI [gastrointestinal] tract or, more rarely, the liver, we generally increase the 2 mgs per kg per day, often giving IV [intravenous] because of how sick the patient is. We have tried to improve upon this but have yet to do so. Unfortunately, about 50% of patients will become steroid-refractory or need a second-line agent. The definitions of “steroid refractory” have traditionally been the following: Either patients get worse in the first 3 days of starting steroids, they don't get better after at least one week, or they do respond yet another organ develops manifestations, or they do respond, and then upon tapering of steroids, their symptoms come back, and they flare. Chronic graft versus host disease (cGVHD) also uses the treatment of systemic steroids. That’s more difficult as well because patients, at that point, months after transplant, have usually experienced some sort of comorbidity and tolerate steroids less well at that point. And chronic graft versus host disease steroids are on for a much longer period of time. The dose is lower. We generally, rather than start at 1 to 2 m gs per kg, we start at maybe half to 1 mg per kg depending on how aggressive we perceive the disease to be. But the fact of the matter is even once chronic graft versus host disease sets in, there is some of it that is likely irreversible organ damage and patients stay on steroids for a very long time. A recent abstract from the Chronic GVHD Consortium would suggest that only a third of patients ever get off steroids for at least a year after starting treatment for chronic graft versus host disease, making it sort of essential that once we start treating patients, we set expectations and understand what in fact we're treating. Research has also gone into trying to improve upon therapy for cGVHD as well, but currently the initial treatment does remain high-dose steroids. Long-term follow-up would show that about 60% of patients that we start steroids on for cGVHD do require a second agent. The definitions of steroid refractory for cGVHD are not as clear cut given the kinetics of the disease and response. In general, for practical purposes, we wait at least 1 to 2 months when starting an agent to determine if patients are refractory to such treatment to add further treatment.

This transcript has been edited for clarity.