A Review of Modern Therapies and New Innovations in the Treatment of Cutaneous Graft-versus-Host Disease

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality following hematopoietic stem cell transplant, with the skin being one of the most common and persistently affected organs in acute and chronic forms of the disease. Topical corticosteroids and supportive dermatologic care are foundational in mild cutaneous disease; however, moderate-to-severe disease frequently requires systemic corticosteroid therapy. Despite systemic corticosteroids being first-line therapy in moderate-to-severe disease, up to 60% of patients will develop steroid-refractory or steroid-resistant disease, emphasizing the need for alternative therapies. Recent advances in GVHD management have led to the introduction of targeted systemic agents, such as ruxolitinib, belumosudil, axatilimab, ibrutinib, and abatacept, each addressing different pathways implicated in disease pathogenesis and leading to incorporation into disease management based on established algorithms or select clinical contexts. Additionally, local immunomodulatory therapies, such as topical ruxolitinib, phototherapies, and extracorporeal photopheresis, can be utilized as adjunctive therapies for persistent or localized cutaneous disease. Cellular therapies, specifically mesenchymal stromal cells and regulatory T cells (Treg), are emerging therapies with promising potential in modulating the immune response and improving clinical outcomes. This review summarizes the current standards of care and recent therapeutic advances in the management of cutaneous GVHD, focusing on evidence-based therapies and skin-specific outcomes.