Real-world toxicity of brexucabtagene autoleucel in adults with relapsed/refractory B-cell acute lymphoblastic leukemia

作者：Noam E. Kopmar, Ted Gooley, Gregory W. Roloff, Amy Zhang, Ibrahim Aldoss, Chenyu Lin, Evandro D. Bezerra, Ibrahim N. Muhsen, Nikeshan Jeyakumar, Kaitlyn C. Dykes, Timothy E. O’Connor, Kevin Tang, Evan C. Chen, Matthew P. Connor, Noelle V. Frey, Christian Gordillo, Talal Hilal, Ali H Al Darobi, Rasmus T. Hoeg, Vivian Michelle Irizarry Gatell, Yannis K. Valtis, Clayton Jackson, Vamsi Kota, Divya Koura, Jacob Boccucci, Caitlin Guzowski, Muthu Sendhil Kumaran, Abdullah Ladha, Catherine J. Lee, Navneet S. Majhail, Shahbaz A. Malik, John Mathews, Katharine Miller, Jozal Moore, Luke Mountjoy, Kristen M. O’Dwyer, María Silvina Odstrcil Bobillo, Caspian Oliai, Olalekan O. Oluwole, Roshini Pradeep, Tamer Othman, Aravind Ramakrishnan, Ran Reshef, Joshua Sasine, Sumithira Vasu, Marc Schwartz, Paul Shaughnessy, Maryann Stefan, Wendy Stock, Katherine C. Sutherland, Virginia Tan, Melhem Solh, Sean Tracy, Marlise R. Luskin, Aaron C. Logan, Jessica Leonard, LaQuisa C. Hill, Stephanie B. Tsai, Anjali S. Advani, Matthew L. Ulrickson, Veronika Bachanová, Bhagirathbhai Dholaria, Jae H. Park, Minoo Battiwalla, Rawan Faramand, Bijal Shah, George Yaghmour, Lori Muffly, Ryan D. Cassaday · 发表于：Blood Immunology & Cellular Therapy · 年份：2025 · DOI：10.1016/j.bict.2025.100028 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Acute Lymphoblastic Leukemia research、Chronic Lymphocytic Leukemia Research

ABSTRACT Brexucabtagene autoleucel (brexu-cel) is an autologous chimeric antigen receptor T-cell (CAR-T) therapy directed to CD19 that is approved for use in adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Pivotal trial data and real-world experience (RWE) studies show high response rates, but also relatively high rates of grade 3+ cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In this RWE study, we sought to better characterize the toxicity profile of brexu-cel in adult patients with R/R B-ALL. To that end, we examined outcomes data from our RWE database for 292 adult patients treated with brexu-cel between October 2021 and June 2024. We found numerically comparable levels of grade 3+ ICANS (28.8%) to those reported on the pivotal ZUMA-3 study, but numerically lower rates of grade 3+ CRS (9.8%). Other clinically-relevant findings included 20.5% requiring intensive care unit-level care, and a rate of death by day +28 post CAR-T of 5.2%. The hazard ratio for death for those with vs. without grade 3+ CRS was 2.24 (95% confidence interval [CI], 1.27-3.94, p=0.005). Compared to those without prior allogeneic transplantation (HCT), the odds of grade 3+ CRS for those with prior HCT was 0.35; (95% CI, 0.14-0.89; p=0.03). While brexu-cel had high response rates in both the trial setting and RWE, our data suggest that severe toxicities (particularly ICANS) remain a distinct challenge with this prod...