Recent FDA Approvals in the Treatment of Graft-Versus-Host Disease

Graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic cell transplantation (HCT) and is associated with significant morbidity and mortality. For many years, there have been few effective treatment options for patients with GVHD. First-line systemic treatment remains corticosteroids, but up to 50% of patients will develop steroid-refractory GVHD and the prognosis for these patients is poor. Elucidation of the pathophysiological mechanisms of acute and chronic GVHD has laid a foundation for novel therapeutic approaches. Since 2017, there have now been 4 approvals by the US Food and Drug Administration (FDA) for GVHD. Ruxolitinib, an oral selective JAK1/2 inhibitor, received FDA approval for the treatment of steroid-refractory acute GVHD in 2019 and remains the only agent approved for acute GVHD. There are currently 3 FDA approvals for the treatment of chronic GVHD: (1) ibrutinib, a BTK inhibitor traditionally used for B-cell malignancies, was the first agent approved for chronic GVHD after failure of one or more lines of systemic therapy, (2) belumosudil, an oral selective inhibitor of ROCK2, for patients with chronic GVHD who received at least 2 prior lines of treatment, and (3) ruxolitinib for chronic GVHD after failure of one or two lines of systemic therapy. In this review, we highlight the clinical data which support these FDA approvals in acute and chronic GVHD with a focus on mechanism of actions, clinical efficacy, and toxicities associated with these agents.