Hematology AdvisorSteroid-Refractory Chronic GVHD: Update on Treatment Options

Evolving Landscape of Chronic Graft-vs-Host Disease: Insights into Pathophysiology and Advancements in Treatment

Chronic graft-vs-host disease (cGVHD) remains a significant challenge in the post-transplant care of patients undergoing allogeneic hematopoietic cell transplantation (aHCT). As the most common long-term complication following aHCT, cGVHD not only impacts patient quality of life but also serves as the leading cause of non-relapse-related morbidity and mortality in long-term survivors. This article provides an in-depth analysis of cGVHD, including its pathophysiology, risk factors, limitations of conventional therapies, and recent advancements in treatment options. Highlighting the increasing incidence of cGVHD and the complexity of its management, the summary underscores the need for a multidisciplinary approach to optimize patient outcomes.

Key Points:

• cGVHD is recognized by its onset post-transplant and affects various organs, significantly impacting patients’ quality of life and survival rates.
• The pathophysiology of cGVHD involves dysregulation of B and T cells, innate immune responses, and a transition from inflammation to fibrosis.
• Risk factors for developing cGVHD include previous acute GVHD, older age, mismatched or unrelated donors, peripheral blood stem cell transplants, male recipients of female donor cells, and donors who are parous women.
• Conventional treatment strategies for mild to severe cGVHD include systemic steroids, calcineurin inhibitors, and other immunosuppressive agents, yet less than 50% of patients respond adequately to first-line treatments.
• Steroid-refractory cGVHD presents a treatment challenge, with no consensus on optimal salvage therapy in the absence of substantial clinical trial data.
• Recent FDA approvals for the treatment of steroid-refractory cGVHD include ruxolitinib, belumosudil, and ibrutinib, each targeting different pathways implicated in the disease’s pathophysiology.
• Ruxolitinib has shown significant efficacy in treating steroid-refractory cGVHD, improving overall response rates and failure-free survival in clinical trials.
• Belumosudil and ibrutinib have also demonstrated high response rates in steroid-refractory cGVHD, with specific considerations for their use based on patient history and disease characteristics.
• Adverse effects commonly associated with these treatments include anemia, thrombocytopenia, and infections, underscoring the importance of careful patient monitoring and management.
• The latest data from the REACH3 trial underscores ruxolitinib’s superiority in controlling cGVHD over best supportive care, offering hope for improved long-term outcomes in this patient population.

HCN Medical Memo
A 2020 study revealed that the use of post-transplant cyclophosphamide as GVHD prophylaxis significantly reduces the incidence of both acute and chronic GVHD without compromising graft-versus-leukemia effects. This approach has been increasingly adopted in haploidentical and unrelated donor transplants, signaling a shift towards less toxic, more effective prophylactic strategies.

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