Real-World Experience With a ZUMA-1 Cohort 4 Adopted Approach to CRS and ICANS in CAR-T Recipients.

Axicabtagene ciloleucel (Axi-cel) is a chimeric antigen receptor T-cell (CAR-T) therapy approved for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The registrational phase 1/2 ZUMA-1 study cohorts 1 and 4 addressed toxicity management in terms of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) whereby tocilizumab and corticosteroids were deployed earlier in cohort 4. In this real-world, single-institution study of 119 patients receiving Axi-cel CAR-T therapy for R/R LBCL with 70 in cohort 1 and 49 in cohort 4, we demonstrate significantly less toxicity, intensive care unit (ICU) utilization, and cumulative steroid use with an early intervention strategy. Laboratory parameters and comorbidities did not significantly differ between groups except for a higher incidence of renal insufficiency in the cohort 4 group (28.6% vs. 4.3%, p < 0.01). The maximum grade CRS was significantly lower for cohort 4 versus 1 (1 vs. 2, p < 0.01). Furthermore, cumulative corticosteroid use was significantly less in the cohort 4 early intervention group (110 mg vs. 190 mg dexamethasone equivalents). These favorable findings did not have a deleterious impact on outcomes and efficacy with similar overall response rate, progression-free survival, and overall survival with both toxicity management approaches.