Advances in Prevention and Treatment Approvals in Chronic GVHD

Advances in Prevention and Treatment Approvals in Chronic GVHD

This segment introduces a medical education discussion on graft-vs-host disease (GVHD) management, focusing on chronic GVHD treatment advances. Two transplant specialists discuss the evolution of care, highlighting significant progress in both prevention and treatment of chronic GVHD. The conversation emphasizes how improved preventive strategies, including posttransplant cyclophosphamide protocols and antibody-based approaches, have reduced severe GVHD incidence while maintaining the need for effective treatments for patients who still develop the condition.

Four FDA-approved agents for steroid-refractory chronic GVHD are reviewed in order of approval: ibrutinib, ruxolitinib, belumosudil, and axatilimab. Ibrutinib, the first approved BTK inhibitor, showed promise in a 42-patient single-arm trial with high complete response rates, though real-world use has been limited by toxicity concerns. Ruxolitinib, a JAK1/JAK2 inhibitor previously used for myeloproliferative diseases, demonstrated efficacy in the randomized REACH-3 trial. Its mechanism involves blocking multiple proinflammatory cytokines (IL-1, IL-6, TNF-α, interferon-gamma) that contribute to GVHD pathogenesis, while also affecting T-cell trafficking and promoting regulatory T-cell function.

Belumosudil represents a novel therapeutic approach, targeting the ROCK2 enzyme pathway. Based on the ROCKstar phase 2 study, which showed approximately 70% overall response rates in patients with moderate to severe chronic GVHD, this agent received FDA approval in 2021. The drug's mechanism involves downregulating inflammatory T-cell subsets (Th17 and T follicular helper cells) that secrete IL-17 and IL-21, while simultaneously upregulating protective regulatory T cells. This selective immune modulation offers a distinct therapeutic mechanism compared with the broader immunosuppressive approaches of previous agents.