Novel Approaches to the Treatment of Chronic Graft-Versus-Host Disease

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.Chronic graft-versus-host disease (cGVHD) is an immune-mediated disease that ensues after allogeneic hematopoietic cell transplantation often affecting multiple organs, decreases quality of life, and necessitates immunosuppressive therapy. The current standard first-line cGVHD therapy is glucocorticoids (GCs) which have major side effects. So far, all attempts to improve response to first-line GC therapy of cGVHD by adding other agents, such as mycophenolate mofetil, or cyclosporine A have not improved response. The data reported in the trial by Miklos et al indicate that ibrutinib should not be added to GC in first-line cGVHD therapy. The findings instruct future studies that aim at the identification of patients with cGVHD who may benefit from a GC-ibrutinib combination using biomarkers or clinical parameters. Currently, ibrutinib, ruxolitinib, and belumosudil are the only drugs that are approved by the Food and Drug Administration for steroid-refractory cGVHD. In light of the current standard management of cGVHD, the trial results indicate that ibrutinib will remain reserved for second-line therapy, which may be due to its mechanisms of action. The recommendation on the basis of this trial is that GC monotherapy remains the standard therapy for cGVHD.