Brexucabtagene autoleucel consolidation in adult B-cell acute lymphoblastic leukemia: real-world efficacy and toxicity

Brexucabtagene autoleucel (brexu-cel), a CD19 chimeric antigen receptor (CAR) T cell is approved for patients with relapsed/refractory B-cell acute lymphoblastic leukemia. In the pivotal ZUMA-3 trial, patients were required to have >5% marrow blasts. We aimed to evaluate efficacy/toxicity with brexu-cel in a real-world setting with marrow blasts of <5%. CAR T-cell levels were assessed in the peripheral blood using flow cytometry. A total of 52 patients were included. The median age was 36.5 years. Patients received a median of 2 previous lines of therapy. At the time of infusion, 14 of 52 patients had next-generation sequencing (NGS) measurable residual disease (MRD)–positive disease; the remaining 38 patients were in NGS MRD–negative remission. The median peak CAR T-cell expansion was 11.5 cells per μL at a median of 8 days after infusion. A peak CAR T-cell expansion threshold of 15 cells per μL was identified as optimal predictor for outcomes. A total of 25 of 52 (48%) patients had a peak CAR T-cell expansion of ≥15 cells per μL and only 4 of 25 (16%) experienced relapse; conversely, 13 of 27 (48%) patients had a relapse among those with peak expansion of <15 cells per μL. With a median follow-up of 24.3 months, 24-month relapse-free survival and overall survival was 59% and 78%, respectively. Grade 3 cytokine release syndrome (CRS) occurred in 1 (2%) patient; grades 3-4 immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 5 (10%) patients. This study highlights CAR T-cell expansion in patients with no morphologic disease, including among patients with NGS-negative remission, and this approach is associated with low rates of grades 3-4 CRS/ICANS.