Cancer Management and Research (Nov 2024)
Clinical Insights on Brexucabtagene Autoleucel for the Treatment of Patients with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia
Abstract
Noam E Kopmar,1,2 Ryan D Cassaday1,2 1Division of Hematology and Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA; 2Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USACorrespondence: Ryan D Cassaday, Clinical Research Division, Fred Hutchinson Cancer Center, 825 Eastlake Ave E, Mailstop LG-700, Seattle, WA, 98109-1023, USA, Tel +1-206-606-6744, Fax +1-206-606-1987, Twitter/X @RyanCassaday, Email [email protected]: Autologous chimeric antigen receptor-modified T-cell therapy (CAR-T) has revolutionized treatment paradigms across multiple lymphoid malignancies, including relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). The introduction of the CD19-directed CAR-T product brexucabtagene autoleucel (brexu-cel; Tecartus) in October 2021 made this treatment approach available for the first time for adults with R/R B-ALL, a historically challenging clinical entity to treat. In this review, we will discuss the pivotal clinical trial data from the ZUMA-3 study that led to the US Food and Drug Administration (FDA) approval of brexu-cel, including clinical outcomes and key toxicity data (most importantly, the incidence and severity of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome). Additionally, we will compare and contrast these data from the ZUMA-3 study with “real-world” data from examinations of patient outcomes with brexu-cel as an FDA-approved therapy in R/R B-ALL, and discuss practical considerations with brexu-cel use in the clinic, including the role of consolidative allografting for patients post-brexu-cel. We finish by discussing future directions for CAR-T use in R/R B-ALL with the anticipated introduction of a new CD19-directed CAR-T product – obecabtagene autoleucel – in the near future.Keywords: brexucabtagene autoleucel, acute lymphoblastic leukemia, adults, chimeric antigen receptor, cellular immunotherapy
