A Critical Review of Clinical Factors and Tools for Predicting Chimeric Antigen Receptor T-Cell Toxicities

Chimeric antigen receptor T (CAR T) cell therapy has improved outcomes in several hematological malignancies but is associated with immune and hematologic toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell-associated hematotoxicity (ICAHT), and immune effector cell-associated hemophagocytosis-like syndrome (IEC-HS). Although diagnostic and grading criteria have been established, there is no consensus on the optimal use of prediction tools. This review describes the incidence of these toxicities and highlights the utility of available tools for predicting and risk-stratifying patients. These studies focus on clinical scores, immunoassays by analyzing CAR T-cell expansion and imaging biomarkers of tumor burden. Among the former, the EASIX score and its derivatives have been validated for predicting severe CRS and ICANS, whereas the CAR-HEMATOTOX score has been validated for predicting prolonged cytopenia. Emerging prediction models aim to integrate these domains to allow early intervention or de-escalation of immunosuppression therapy.