Noncanonical and mortality-defining toxicities of CAR T cell therapy



Summary

CAR T-cell therapy, while revolutionary, can trigger severe toxicities beyond the well-known cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). These less recognized, “noncanonical” toxicities can significantly impact patient outcomes and even lead to death. Examples include prolonged cytopenias, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), atypical neurotoxicities, cardiac dysfunction, and immune-mediated complications like colitis and hypogammaglobulinemia. These often arise due to off-target effects, pre-existing conditions, or exaggerated immune responses. Early identification and aggressive management are crucial to mitigating these potentially life-threatening complications and improving the safety profile of CAR T-cell therapy.

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