Real-world outcomes for young adult patients receiving CD19 CAR T-cell therapy
Hannah Lust, Liora M. Schultz, Soyang Kwon, Gregory W. Roloff, Ibrahim Aldoss, Christina Baggott, Samuel John, Jenna Rossoff, Kevin O. McNerney, Vanessa A. Fabrizio, Julie-An Talano, Amy Moskop, Kevin J. Curran, Christine L. Phillips, Nicole Karras, Susanne H.C. Baumeister, Stacy Cooper, Michelle L. Hermiston, Prakash Satwani, Muna Qayed, Sunil S. Raikar, Margaret L. MacMillan, Erin Hall, Khanh Nguyen, Ryan D. Cassaday, Noam E. Kopmar, Vamsi Kota, John Mathews, Paul Shaughnessy, Marc S. Schwartz, Abdullah Ladha, George Yaghmour, Muthu Sendhil Kumaran, Veronika Bachanová, Sean Tracy, Tamer Othman, Marlise R. Luskin, Evan C. Chen, Anjali S. Advani, Nikeshan Jeyakumar, Katharine Miller, Amy Zhang, Katherine C. Sutherland, Bijal Shah, Lori Muffly, Rawan Faramand
Abstract
ABSTRACT: Tisagenlecleucel (tisa-cel) and brexucabtagene autoleucel (brexu-cel) are approved CD19 chimeric antigen receptor T-cell therapy (CAR T) products for young adults (YA) with relapsed/refractory B-cell acute lymphoblastic leukemia. A distinct analysis of YAs receiving commercial CD19 CAR T has not been reported. Using retrospective data from the Pediatric Real-World CAR T Consortium and the Real-World Outcomes of CAR T in Adult ALL collaboration, we describe the efficacy and safety of tisa-cel and brexu-cel in 70 YAs (18-26 years; tisa-cel, n = 50; brexu-cel, n = 20). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were observed more frequently for brexu-cel vs tisa-cel (CRS, 85% vs 56%; ICANS, 40% vs 18%). Complete response rates were similar between products at 80% for brexu-cel and 88% for tisa-cel. Relapse-free survival (RFS) at 12 months was 46% for brexu-cel and 36% for tisa-cel. Durability of remission over 12 months was 61% for brexu-cel vs 41% for tisa-cel; 12-month overall survival (OS) for brexu-cel was 84% vs 68% for tisa-cel. In multivariate analysis, low disease burden was associated with improved OS, whereas inotuzumab before CAR T was associated with inferior outcomes. This study demonstrates comparable real-world efficacy among YAs receiving CD19 CAR T irrespective of CAR T construct; however, rates of toxicity seem higher with brexu-cel.