CAR-T cell therapy – toxicity and its management

Chimeric antigen receptor T-cell (CAR-T) therapy is an effective new treatment for hematologic malignancies. Two anti-CD19 CAR-T products, namely axicabtagene ciloleucel and tisagenlecleucel, have been approved for the management of relapsed/refractory large B-cell lymphoma after two lines of systemic therapy. Additionally, tisagenlecleucel is indicated for refractory acute lymphoblastic leukemia in pediatric patients and young adults up to 25 years of age. CAR-T cells are undoubtedly a major breakthrough therapy in hematooncology resulting in up to 90% response rate with durable remissions in population with refractory high-risk disease. However, there are serious side effects resulting from CAR-T therapy, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Manifestations of CRS mostly include fever, hypotension, hypoxia, and end organ dysfunction. Neurologic toxicities are diverse and include encephalopathy, cognitive defects, dysphasia, seizures, and cerebral edema. Since the symptoms are potentially severe, practitioners need to familiarize themselves with the unique toxicities associated with these therapies. In this article, we present a practical guideline for diagnosis, grading and management of CRS and CAR-T neurotoxicity. In addition, infectious complications and late toxicities including prolonged cytopenias and hypogammaglobulinemia are discussed.