CELL INTELLIGENCE · 肿瘤细胞治疗研究

While cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are well-recognized toxicities of CAR T-cell therapy, immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) remains poorly characterized. We aimed to describe the incidence, clinical features, management, and outcomes of IEC-HS using real-world data from the DESCAR-T registry (NCT04328298). We conducted a multicenter retrospective study of patients registered in DESCAR-T who received standard-of-care CD19 CAR T-cell therapy for relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) or B-cell acute lymphoblastic leukemia (B-ALL) and fulfilled ASTCT criteria for IEC-HS. We analyzed 42 patients who developed IEC-HS. Most had a high CAR-HEMATOTOX score ( 2, n = 36) and prior high-grade CRS (grade 3, n = 20). IEC-HS was characterized by marked hyperinflammation, with high median ferritin (18,561 g/L), lactate dehydrogenase (825 IU/L), and triglycerides (4.5 g/L), and low fibrinogen (0.9 g/L). Median time to IEC-HS onset was 9 days (IQR 6-21). Patients received a median of two treatment lines. Observed response rates were 77% with etoposide, 70% with corticosteroids, 70% with corticosteroids plus anakinra, and 50% with tocilizumab, with combination therapy more frequently used in severe cases. After a median follow-up of 24.1 months, overall mortality was 81%. One-year overall survival was 15.6% for B-NHL and 47.1% for B-ALL. In this real-world cohort, IEC-HS was a rare but life-threatening complication of CD19 CAR T-cell therapy, often occurring after severe CRS and associated with poor outcomes. Despite initial inflammatory control, mortality remained high, underscoring the need for improved risk stratification and management strategies.