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

ABSTRACT 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.