Treatment Options in Steroid-Refractory Chronic GVHD: Mechanisms, Evidence, and Trade-Offs

This segment surveys the systemic and non-pharmacologic options available once chronic GVHD becomes steroid refractory, comparing them across mechanism, supporting evidence, and clinical trade-offs. Faculty review the currently approved therapies, each acting through a distinct pathway: ibrutinib targeting BTK and ITK signaling, ruxolitinib inhibiting the JAK pathway, belumosudil acting on ROCK2 across inflammatory and sclerotic disease, and axatilimab, a CSF1R-directed antibody aimed at the monocyte and macrophage drivers of fibrosis. The discussion connects each agent to its pivotal evidence, including REACH3 for ruxolitinib and ROCKSTAR for belumosudil, and highlights durable responses, steroid sparing, and activity across organ systems. Extracorporeal photopheresis is discussed as a non-pharmacologic approach that may help reset T-cell activity, with candid acknowledgment of mixed real-world experience. Throughout, faculty emphasize matching mechanism to the individual patient, weighing prior exposure, tolerability, and disease phenotype when sequencing later-line therapy.