Hematology AdvisorSteroid-Refractory Chronic GVHD: Update on Treatment Options

Unveiling the Pathophysiology and Advancing Treatment Strategies for Steroid-Refractory Chronic GVHD

Graft-vs-host disease (GVHD) stands as a significant complication post-allogeneic hematopoietic cell transplantation (aHCT), with its chronic form, cGVHD, manifesting as a major long-term challenge. This article looks into the intricate pathophysiology of steroid-refractory cGVHD, highlights the limitations of conventional therapies, and elucidates the recent advancements in treatment options, including FDA-approved therapies, thereby offering new horizons for patient management and care.

Key Points:

• cGVHD is a common long-term complication post-aHCT, affecting multiple organs and significantly impairing quality of life.
• The pathophysiology of cGVHD involves dysregulation of B and T cells and a transition from inflammation to fibrosis, indicating a complex interplay of immune responses.
• Risk factors for cGVHD include prior aGVHD, older age, mismatched/unrelated donors, and stem cell source, among others.
• Conventional therapy for moderate to severe cGVHD includes high-dose steroids and calcineurin inhibitors, but less than 50% of patients respond adequately.
• Steroid-refractory cGVHD is defined by progression or lack of response to high-dose steroids, with treatment being highly individualized due to varied patient responses.
• Advancements in treatment include FDA-approved therapies like ruxolitinib, belumosudil, and ibrutinib, each targeting different pathways implicated in cGVHD.
  • Ruxolitinib has demonstrated superiority in response rates and failure-free survival compared to best supportive therapy in clinical trials.
  • Belumosudil showed high response rates in patients, including those who had prior treatment with ruxolitinib or ibrutinib.
  • Ibrutinib, the first FDA-approved therapy for cGVHD, has shown effective responses in organ involvement and sclerotic features.
• Ongoing research and clinical trials continue to refine the understanding and management of steroid-refractory cGVHD, highlighting the need for personalized treatment approaches.

More than 26,000 allogeneic hematopoietic cell transplantations (alloHCTs)are performed annually worldwide.

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