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000302989 1001_ $$00000-0003-3905-0251$$aRejeski, Kai$$b0
000302989 245__ $$aNoncanonical and mortality-defining toxicities of CAR T cell therapy.
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000302989 520__ $$aChimeric antigen receptor (CAR) T cell therapy is associated with a unique spectrum of toxicities that drive morbidity, mortality and patient quality of life. Previous efforts yielded consensus grading systems for the prototypical immunotoxicities-namely, cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). These grading systems set the stage for severity-based and standardized treatment protocols that have contributed to a reduction in the acute toxicity burden of CAR T cell therapy and have enabled outpatient administration. However, understanding of CAR T cell therapy has since grown to encompass new targets, new diseases and broader patient populations-including long-term survivors. As side effects are better defined and novel toxicities emerge, there is a need to understand their mechanisms and standardize reporting to improve clinical management. Here we review the current state of knowledge for mortality-defining and rare toxicities of CAR T cell therapies, beyond CRS and ICANS. We discuss mechanisms, including on-target injury, cytokine-associated inflammation and dysregulated recovery, and how these mechanisms affect the timing and management of toxicities. Finally, we define key unmet needs and delineate future priorities and research directions.
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000302989 7001_ $$00000-0002-7665-7100$$aHill, Joshua A$$b1
000302989 7001_ $$aDahiya, Saurabh$$b2
000302989 7001_ $$00000-0002-7789-1257$$aJain, Michael D$$b3
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