Curr Opin Immunol. 2025 Aug 26;96:102649. doi: 10.1016/j.coi.2025.102649. Online ahead of print.
ABSTRACT
Acute graft-versus-host disease (aGVHD) is a significant complication of allogeneic hematopoietic cell transplantation (allo-HCT), characterized by immune-mediated tissue damage from donor immune cells. Standard treatment of aGVHD involves systemic corticosteroids, but many patients do not respond adequately, with 30%-50% of patients being steroid refractory (SR-aGVHD) leading to poor outcomes. This highlights the need for effective second-line therapies. Ruxolitinib, a JAK1/2 inhibitor, has emerged as a key treatment, demonstrating superior overall response rates in SR-aGVHD compared to best available therapies. However, resistance and intolerance to ruxolitinib necessitate exploring novel and combination therapies such as apraglutide, neihulizumab, and other targeted agents, which have shown promising results in clinical trials. Additionally, nonpharmacologic approaches, including microbiotherapy, mesenchymal stromal cells, or alpha-1 antitrypsin, are also being investigated for their immunomodulatory potential. The future direction is to develop personalized treatment strategies that incorporate biomarkers and diverse therapeutic modalities. The aim is to enhance disease management, aiming for sustainable control and improved quality of life in patients facing the challenges of SR-aGVHD.
PMID:40865409 | DOI:10.1016/j.coi.2025.102649