In an analysis reported in the Journal of Clinical Oncology, Roloff et al found that use of brexucabtagene autoleucel as standard therapy in adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) was associated with a high rate of measurable residual disease (MRD)-negative complete remissions.
As stated by the investigators, “On the basis of the results of the ZUMA-3 trial, … [brexucabtagene autoleucel], a CD19-directed chimeric antigen receptor T-cell therapy, gained U.S. Food and Drug Administration approval in October 2021 for adults with … [relapsed/refractory] B-ALL. We report outcomes of patients treated with [brexucabtagene autoleucel] as a standard therapy.”
Key Findings
The study involved data from a collaboration across 31 U.S. centers (ROCCA consortium) on patients with B-ALL receiving brexucabtagene autoleucel outside the context of a clinical trial. At the time of data lock, 204 patients had undergone apheresis and 189 received brexucabtagene autoleucel infusion. Median follow-up was 11.4 months. A total of 42% of patients received brexucabtagene autoleucel in morphologic remission and thus would have been ineligible for inclusion in ZUMA-3.
Among 168 patients evaluable for response at day 28 following brexucabtagene autoleucel therapy, 151(90%) achieved complete remission, with 119 (79%) of these being MRD-negative remission. Among the 151 patients with complete remission, median progression-free survival was 9.5 months, with rates at 6 and 12 months of 59% and 48%. Median overall survival was not reached, with rates at 6 and 12 months of 78% and 63%.
On multivariate analysis, patients receiving consolidative hematopoietic cell transplantation after brexucabtagene autoleucel had improved progression-free survival vs those with no consolidation or maintenance therapy (hazard ratio = 0.34, 95% confidence interval [CI] = 0.14–0.85).
Grade 3 or 4 cytokine-release syndrome occurred in 11% of patients, and grade 3 or 4 immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 31%. A total of 10 patients (5.3%) died from toxicity or infection within the first 28 days; 9 of 10 had grade 4 cytokine-release syndrome or grade 4 ICANS preceding death.
The investigators concluded: “Similar to ZUMA-3, high rates of MRD-negative [complete remission] were observed after [brexucabtagene autoleucel] treatment for [relapsed/refractory] B-ALL. The use of [hematopoietic cell transplantation] as consolidation after [brexucabtagene autoleucel] resulted in improved [progression-free survival].”
Lori Muffly, MD, MS, of the Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
