Emapalumab for Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome Following CD19-Directed CAR-T in Two Patients With B-ALL: Clinical and Biomarker Correlates.

Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) is a life-threatening hyperinflammatory toxicity distinct from cytokine release syndrome (CRS) and neurotoxicity following chimeric antigen receptor T-cell (CAR-T) therapy. In a single-institution retrospective cohort of pediatric and young adult patients with relapsed or refractory acute B-lymphoblastic leukemia (B-ALL) treated with tisagenlecleucel between November 2023 and April 2025, two of 12 patients (17%) developed IEC-HS after CRS resolution, marked by recurrent fever, coagulopathy, hepatic dysfunction, cytopenias, and profound elevations in CXCL9, IL-18, and soluble C5b-9. Treatment with emapalumab led to rapid clinical and biomarker improvement. These findings support IEC-HS as an interferon-γ-driven syndrome and suggest targeted IFN-γ blockade as a potentially effective therapeutic strategy.