Exploratory study of PD-1 inhibitors with or without ruxolitinib for the treatment of adult EBV-associated hemophagocytic lymphohistiocytosis: a real-world data-based preliminary investigation.

To preliminarily analyze the clinical efficacy and safety of PD-1 inhibitors as monotherapy or in combination with ruxolitinib (RUX) for adult Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) based on real-world retrospective data. A retrospective case series analysis was performed on clinical data of 4 adult EBV-HLH patients treated with sintilimab (a PD-1 inhibitor) alone or combined with RUX at the Department of Hematology, Hunan Provincial People’s Hospital, from April 1, 2020 to February 1, 2024. Clinical efficacy, survival outcomes, dynamic changes of laboratory indicators and adverse reactions were observed. Among the 4 patients, 2 achieved complete remission (CR), 1 experienced treatment interruption due to non-adherence and was lost to follow-up, and 1 died of multi-organ failure induced by COVID-19, with a 1-year overall survival (OS) rate of 75.00%. All patients received sintilimab with a median treatment course of 9.5 cycles and a median infusion dose of 1900 mg; 3 patients were combined with RUX. After one cycle of treatment, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and interleukin-10 (IL-10) decreased significantly, while white blood cell (WBC), hemoglobin (HGB) and platelet (PLT) levels increased significantly (all  < 0.05). Ferritin (Ferr) returned to the normal range and fibrinogen (Fbg) showed an upward trend. The number of peripheral blood T, B and natural killer (NK) cells increased in 3 patients who completed lymphocyte subset detection. No drug-related severe adverse reactions of grade 3 or above were observed in all patients. PD-1 inhibitors alone or combined with RUX show preliminary favorable efficacy and high tolerability in the treatment of adult EBV-HLH, which can effectively improve blood cell levels, control inflammatory responses and increase clinical remission rates. However, large-sample prospective studies are required to verify the long-term efficacy due to the small sample size of this study.