Extracorporeal photopheresis alone or in combination with ruxolitinib for the treatment of chronic graft-versus-host disease

Chronic graft-versus-host disease (cGvHD) is a major cause of morbidity after allogeneic hematopoietic stem cell transplantation. Ruxolitinib (RUX) is a standard second-line treatment for steroid-refractory or -dependent cGvHD, while extracorporeal photopheresis (ECP), an autologous cell-based immunomodulatory procedure, is also widely used. However, comparative real-world data on combined immunomodulation with the RUX-ECP combination are scarce. We conducted a retrospective single-center analysis of patients with steroid-refractory or -dependent cGvHD receiving RUX-ECP (n=30) or ECP alone (n=21) between 2012 and 2025. The overall response rate was 77% with RUX-ECP and 52% with ECP (p=0.13), with CR rates of 17% and 10% (p=0.69). RUX-ECP was associated with a significantly shorter time to first response (2.6 vs. 12.3 months, p=0.0249). Organ-specific trends favored RUX-ECP in gastrointestinal, ocular and cutaneous cGvHD, whereas both regimens showed limited activity in pulmonary disease. Overall survival, relapse incidence and non-relapse mortality were comparable. At 12 months, complete steroid discontinuation (69% vs. 10%; p=0.005) and relative corticosteroid reduction were significantly greater with RUX-ECP (88% vs. 30%; p=0.0026). Toxicities of RUX-ECP were manageable and consistent with the known RUX profile, and several patients discontinued therapy after stable responses. Thus, combined immunomodulation with RUX-ECP showed high and fast response rates, a favorable safety profile and substantial steroid-sparing, supporting further evaluation in steroid-refractory or -dependent cGvHD patients.