早期使用类固醇和阿那白滞素管理 axicabtagene ciloleucel 毒性可缩短 CRS 和 ICANS 的总持续时间

Axicabtagene ciloleucel (axi-cel) is an effective chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory (R/R) large B-cell lymphoma (LBCL).

However, 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.

To evaluate this change, we conducted a retrospective analysis of patients receiving axi-cel for R/R LBCL in the third-line setting from January 2018 through April 2023. The outcomes of interest were toxicity incidence/duration, treatment response, CAR-T expansion, and drug/health care utilization. Of the 195 identified patients, the postchange cohort (n = 103) had higher rates of anakinra (22% vs 5%) and steroid use (88% vs 71%) use 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 postchange cohort. A significant reduction in CRS and ICANS duration was observed with the new protocol (adjusted estimate, -0. 93 days [95% confidence interval (CI), -1. 67 to -0. 19] and -2. 49 days [95% CI, -4. 96 to -0. 03], respectively). Day 7 CAR-T expansion was lower in the postchange cohort, possibly due to earlier steroid use.

However, efficacy outcomes, intensive care unit 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.