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Chimeric antigen receptor T-cell (CAR-T) therapy has proven to be a very effective cancer immunotherapy. Axicabtagene ciloleucel and tisagenlecleucel are the first-in-class anti-CD19 CAR-T currently available for relapsed/refractory adult large B-cell lymphoma. Tisagenlecleucel is also available for pediatric and young adult (up to age 25 years) patients with relapsed/refractory B-acute lymphoblastic leukemia. Cytokine release syndrome (CRS) and CAR-T-associated encephalopathy syndrome (neurotoxicity) are the most common adverse effects associated with CAR-T therapy. They can lead to significant morbidity and preclude widespread use of this treatment modality. Treatment-related deaths from severe CRS and cerebral edema have been reported. There is a significant heterogeneity in the side-effect profile of different CAR-T products under investigation and there is a need to develop standardized guidelines for toxicity grading and management. Here, we summarize the current literature on pathogenesis, clinical presentation, and management of CRS and neurotoxicity. The different grading systems of CRS and management protocols used in different trials have made it difficult to compare the outcomes of different CAR-T therapies. Several prevention strategies such as predictive biomarkers of CRS and neurotoxicity and modified CAR-T with 'built-in' safety mechanisms are being studied, with the potential to greatly expand the safety and applicability of CAR-T treatment across various malignancies. [ABSTRACT FROM AUTHOR]

Adoptive T-cell immunotherapy is a rapidly growing field and is shifting the paradigm of clinical cancer treatment. Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor T-cell therapy that was initially developed at the National Cancer Institute and has recently been commercially approved by the US Food and Drug Administration for relapsed or refractory aggressive non-Hodgkin's lymphomas including diffuse large B-cell lymphoma and its variants. The ZUMA-1 Phase I and II clinical trials formed the basis of the US Food and Drug Administration approval of this product, and we discuss the particulars of the clinical trials and the pharmacology of axi-cel. In addition, we review the CD19 chimeric antigen receptor T-specific toxicities of cytokine release syndrome and neurotoxicity, which remain the challenges to the safe delivery of this important therapy for aggressive B-cell lymphomas with poor prognosis. [ABSTRACT FROM AUTHOR]