Managing Treatment-Emergent Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome Following CAR-T Cell Therapy: A Case-Based Review of the use of Emapalumab.

Chimeric antigen receptor T (CAR-T) cell therapies have revolutionized the treatment of hematological malignancies, achieving high response rates in patients with relapsed or refractory disease. Despite these benefits, CAR-T cell therapies are associated with unique toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), immune cell-associated hematotoxicity (ICAHT), and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), which is characterized by a rare and life-threatening hyperinflammatory response. This paper presents a case of a 56-year-old woman with relapsed mantle cell lymphoma (MCL) treated with the CAR-T cell therapy, brexucabtagene autoleucel, who had subsequently developed CRS and later IEC-HS. Initial management included tocilizumab, corticosteroids, and anakinra, followed by the compassionate use of emapalumab, an interferon-γ blocker. To provide broader context, we conducted a literature review of CAR-T cell-related toxicities, focusing on IEC-HS and its management with emapalumab. Clinical and laboratory manifestations, such as elevated ferritin levels, cytopenias, and organ dysfunction, underpin the diagnostic criteria for IEC-HS. Vigilant monitoring and tailored therapeutic approaches are required to effectively manage toxicities associated with CAR-T cell therapy, to maximize its benefits and minimize adverse effects. In more severe IEC-HS cases, emapalumab may be used as an effective targeted therapy.