ZUMA-8: a phase 1 study of brexucabtagene autoleucel in patients with relapsed/refractory chronic lymphocytic leukemia

ABSTRACT: ZUMA-8 evaluated the safety of brexucabtagene autoleucel (brexu-cel), a CD19-directed autologous chimeric antigen receptor (CAR) T-cell immunotherapy, for patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Patients with ≥2 prior lines of therapy (including a Bruton tyrosine kinase inhibitor) underwent leukapheresis, optional bridging therapy, and conditioning chemotherapy (fludarabine/cyclophosphamide) before infusion of 1 × 106 (cohort 1) or 2 × 106 (cohort 2) anti-CD19 CAR T cells per kg. Patients in cohort 3 (low tumor burden), and cohort 4A (postibrutinib) received 1 × 106 cells per kg. Fifteen patients, median age of 63 years (range, 52-79), were treated in cohorts 1 (n = 6), 2 (n = 3), 3 (n = 3), and 4A (n = 3). Median follow-up was 24.3 months. One dose-limiting toxicity was observed in cohort 3 (grade 4 cytokine release syndrome). Grade ≥3 neurologic events occurred in 3 patients (20%). Seven of 15 patients responded (overall response rate, 47%; complete response [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 before apheresis. Brexu-cel had no new safety signals in R/R CLL. CAR T-cell expansion and responses occurred in patients with low tumor burden. This trial was registered at www.clinicaltrials.gov as #NCT03624036.