Major Adverse Events With Chimeric Antigen Receptor T-Cell Therapy: Presentation, Diagnosis, and Resuscitation

With continued advances in targeted cancer treatment, such as chimeric antigen receptor T-cell (CAR-T) therapy, emergency departments (EDs) across the United States should be prepared to diagnose and care for patients who experience unique adverse events related to CAR-T administration. CAR-T therapy is the first genetically modified cellular therapy approved by the Food and Drug Administration for treatment of several hematologic malignancies, including leukemia, lymphoma, and myeloma. The side effect profile differs from conventional chemotherapy and consists of a spectrum of immune-mediated clinical manifestations, particularly cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and the more recently described immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. Cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome can present with nonspecific symptoms and signs and should be differentiated from other life-threatening pathologies such as sepsis and meningitis. There is limited guidance for emergency physicians and staff regarding the recognition and management of CAR-T complications, both in adult and pediatric patient care settings. This clinical review provides insight into the common and less common CAR-T toxicities, including symptomatology, diagnostic approach, and fundamental principles of complication management in adult and pediatric patients undergoing CAR-T therapy.