Corey S. Cutler, MD, MPH, FRCPC: What are the treatment options for this patient? This case is de novo chronic graft-versus-host disease [GvHD], and the standard of care is to treat with corticosteroids. Steroids are generally given at a dose of 0.5 to 1 mg/kg of body weight, usually 0.5 mg/kg per day or 1 mg/kg every other day. However, some clinicians will start at a dose of 1 mg/kg per day. In general, doses higher than that are not recommended in chronic graft-versus-host disease. There is some evidence that adding a calcineurin inhibitor at the onset of chronic GvHD might decrease steroid burden over time, although it does not increase response rates. Some of us clinicians will add drugs like tacrolimus or cyclosporine at the time of initial therapy for chronic graft-versus-host disease.
For chronic GvHD, most of us will treat at a minimum for 4 weeks at a single steroid dose, and up to 3 months has been often the classic teaching in this disease. We generally wouldn’t consider someone steroid-refractory unless they were progressing after several weeks of therapy or really had no response after a good trial of 2 to 3 months of therapy. There are certain clinical scenarios, particularly those that are involving scleroderma or progressive lung disease that merit earlier switch to a second-line agent.
In terms of the drugs that we use for the second-line setting, there’s only 1 drug that is approved at this point and that is ibrutinib. Ibrutinib is approved based on a 42-patient study done, an open-label phase 2 trial that demonstrated a response rate of about two-thirds in patients with steroid-refractory chronic graft-versus-host disease. So ibrutinib is the de facto second-line agent. We also recommend participation in clinical trials whenever possible, and there are a number of exciting compounds that are being tested these days for second-line therapy and beyond for chronic graft-versus-host disease.
Transcript edited for clarity.
Case: A 49-Year-Old Man With Steroid-Refractory Chronic Graft Versus Host Disease