Latest updates on pathogenesis mechanisms and management strategies for cytokine release syndrome, neurotoxicity, and hemophagocytic lymphohistiocytosis related to CAR-T cell therapies.

Nowadays, chimeric antigen receptor (CAR) -T cell therapy has shown significant efficacy in treating hematological tumors, with an obvious increase in patient survival rates. However, with the widespread application of CAR-T, the incidence of CAR-T related adverse events has gradually increased, including cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), and hemophagocytic lymphohistiocytosis (HLH). These complications may be life-threatening, so early diagnosis and intervention treatment are crucial for the prognosis of patients. In this review, we first comprehensively summarize the latest insights into the pathogenesis and clinical manifestations of CRS, ICANS, and HLH after CAR-T, with a focus on elaborating on the specific mechanisms and related pathways of the inflammatory storm caused by a large number of cytokines after CAR-T. We also discussed the established prevention and management strategies for the three complications mentioned above, and demonstrated the effectiveness of the treatment by introducing the therapeutic effects of various treatment methods in current clinical or preclinical trials. In addition, we provide a prospective perspective on the measures and modifications currently being studied to mitigate the toxicity associated with CAR-T cell therapy.