Early Steroid and Anakinra Use to Manage Axicabtagene Ciloleucel Toxicity Reduces the Total Duration of CRS and ICANS

Axicabtagene ciloleucel (axi-cel) is an effective CAR-T cell therapy for relapsed or refractory (R/R) large B-cell lymphoma (LBCL). Yet, controlling cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) without compromising therapeutic efficacy remains a difficult challenge. In July 2020, our center adopted a toxicity management protocol modified from Cohort 4 of the registrational ZUMA-1 trial, with earlier steroid use and incorporation of anakinra in toxicity management. To evaluate this change, we conducted a retrospective analysis of patients receiving axi-cel for R/R LBCL in the 3L+ setting from January 2018 through April 2023. The outcomes of interest were toxicity incidence/duration, treatment response, CAR-T expansion, and drug/healthcare utilization. Out of the 195 identified patients, the post-change cohort (N = 103) had higher anakinra (22% vs. 5%) and steroid (88% vs. 71%) usage rates than the comparator cohort (N = 92) without increases in cumulative steroid dose. Overall CRS and ICANS rates were similar, with directionally lower severe (grade 3+) ICANS rates in the post-change cohort. A significant reduction in CRS and ICANS duration was observed with the new protocol (adj. est: -0.93 [95% CI: -1.67, -0.19] days and -2.49 [95% CI: -4.96, -0.03] days, respectively). Day 7 CAR-T expansion was lower in the post-change cohort, possibly due to the earlier steroid use. However, efficacy outcomes, ICU admission rates, and hospitalization length were similar between the cohorts. This study supports earlier intervention for CAR-T toxicities and establishes anakinra as a safe and effective alternative toxicity management drug to tocilizumab.