CRS and ICANS: Early detection and personalized management

T-cell–redirected immunotherapies, including chimeric antigen receptor T-cell therapy and bispecific antibodies, have transformed the treatment of relapsed or refractory hematologic malignancies. However, cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) remain the major immune-mediated toxicities that can complicate treatment delivery and contribute to morbidity and non-relapse mortality. CRS is characterized by systemic inflammatory amplification involving activated T cells, tumor cells, monocytes/macrophages, endothelial activation, and cytokine networks. ICANS is biologically related to CRS but has distinct features, including endothelial injury, blood–brain barrier disruption, and central nervous system inflammation. Standardized grading systems and structured neurologic assessments provide a common framework for recognition; however, optimal care increasingly requires risk-adapted and individualized strategies. Baseline disease burden, systemic inflammation, endothelial vulnerability, organ reserve, treatment platform, and product-specific toxicity profiles may help identify patients requiring closer monitoring or earlier intervention. Although prediction models and emerging monitoring approaches may improve early recognition, their roles should complement rather than replace clinical judgment. Management should balance timely toxicity control with the preservation of antitumor efficacy, avoidance of excessive immunosuppression, and careful attention to infection and cytopenia risks. For refractory CRS or ICANS, phenotype-directed escalation and multidisciplinary care are essential. This review summarizes the current concepts in the biology, recognition, risk prediction, early detection, and personalized management of CRS and ICANS.