Simple and early prediction of severe CAR-T-related adverse events after Axi-cel infusion by initial high fever

Chimeric antigen receptor T-cell (CAR-T)-related adverse events (CAR-AEs), such as immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS), can be life-threatening and may require high-dose steroids. Identifying patients at high risk for severe CAR-AEs in a simplified way is crucial for early therapeutic intervention. This retrospective study analyzed 44 patients treated with axicabtagene ciloleucel (Axi-cel) to identify predictive factors for severe CAR-AEs. We found that grade ≥ 3 ICANS, hemophagocytic syndrome, and ICU admission were associated with a greater need for high-dose steroids, which we defined as events associated with high-dose steroids (EHS). The incidence of EHS was significantly higher in patients who developed an initial fever (≥ 38.6 °C) within 24 h of CAR-T infusion (p < 0.001). Progression-free survival (PFS) was significantly shorter in patients with EHS compared to those without EHS (p < 0.001). Additionally, patients who developed a fever within 24 h and those with a peak fever of ≥ 38.6 °C both tended to have higher peak CAR-T counts compared to other patients. Our findings suggest that an initial fever (≥ 38.6 °C) within 24 h of Axi-cel infusion may predict severe CAR-AEs requiring high-dose steroids, and that EHS is associated with worse PFS.