ZUMA-8: A Phase 1 Study of Brexucabtagene Autoleucel in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia

• The safety profile of brexucabtagene autoleucel in relapsed refractory CLL was similar as in the currently approved indications

• In vivo expansion of cells and clinical activity were suboptimal and were observed mainly in patients with low disease burden.

Abstract ZUMA-8 (NCT03624036) is the first prospective trial to evaluate the safety of brexucabtagene autoleucel (previously KTE-X19), a CD19-directed autologous CAR T-cell immunotherapy, in patients with R/R CLL. Patients with ≥2 prior lines of therapy (including a BTK inhibitor) underwent leukapheresis, followed by optional bridging therapy, then conditioning chemotherapy (fludarabine/cyclophosphamide) before infusing 1×106 (Cohort 1) or 2×106 (Cohort 2) anti-CD19 CAR T cells/kg. Patients in Cohort 3 (low tumor burden), and Cohort 4A (ibrutinib pre-treated closely to the apheresis) received 1×106 cells/kg. Fifteen patients, median age 63 years (52-79 years), were treated in Cohort 1 (n=6), Cohort 2 (n=3), Cohort 3 (n=3), and Cohort 4A (n=3). Median follow-up was 24.3 months. One DLT was observed in Cohort 3 (n=1 grade 4 cytokine release syndrome). Grade ≥3 neurologic events occurred in 3 patients (20%). Seven of 15 patients responded (ORR 47%, CR 7%), including all 3 patients in cohort 3 (1 with CR). CAR T-cell expansion occurred in 4 patients (27%), with an apparent weak inverse correlation with absolute lymphocyte count (ALC) prior to the apheresis. Brexu-cel did not have any new safety signals in R/R CLL, and CAR T-cell expansion and responses occurred in patients with low tumor burden.