Five-year follow-up of patients with relapsed/refractory mantle cell lymphoma treated with anti-CD19 CAR T-cell therapy in ZUMA-2, Cohorts 1 and 2
Year: 2026
Type: article
Abstract: Background Treatment with brexucabtagene autoleucel (brexu-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated a high objective response rate (93%) and complete response rate (67%) in 60 patients with relapsed/refractory mantle cell lymphoma (R/R MCL) treated in the pivotal ZUMA-2 Cohort 1 study. Subsequently, brexu-cel was approved in the United States and European Union for the treatment of adults with R/R MCL (after ≥ 2 prior therapies in the European Union). Here we report 5-year outcomes from the pivotal ZUMA-2 Cohort 1 study ( N = 68), as well as two previously unpublished ZUMA-2 data sets, long-term outcomes in 10 patients who received axi-cel in Cohort 1 and in 14 patients who received a lower dose of brexu-cel in Cohort 2. Methods The primary endpoint for all cohorts of ZUMA-2 was objective response rate. Key secondary endpoints included duration of response (DOR), overall survival (OS), and safety. Patients could transition to a long-term follow-up study after 24 months for monitoring of survival and select adverse events possibly related to brexu-cel. Patients in Cohort 1 received a single infusion of 2 × 10 6 anti-CD19 CAR T cells/kg (axi-cel or brexu-cel). Patients in Cohort 2 received 0.5 × 10 6 anti-CD19 CAR T cells/kg (brexu-cel). Results Median follow-up for the pivotal cohort ( N = 68) was 67.8 months (range, 58.2–88.6) with a median DOR of 36.5 months ( n = 60), per investigator review. Median OS was 46.5 months (95% CI, 24.5–60.2; N = 68) and was 60.2 months (95% CI, 42.8-not estimable) in patients with complete response ( n = 46). The 5-year incidence of cumulative relapse-related and non-relapse–related mortality was 40% (24/60) and 22% (13/60) in responders, respectively. Descriptive outcomes for axi-cel–treated patients ( N = 10) and Cohort 2 ( N = 14) are reported herein. No Grade 5 cytokine-release syndrome or neurologic events, subsequent T-cell malignancies, or new safety signals were reported in any patient. Conclusions Patients in ZUMA-2 continued to have durable responses after 5 years of follow-up with predictable long-term safety, supporting the continued use of brexu-cel in R/R MCL. Interpretations of outcomes in axi-cel–treated patients and Cohort 2 are not feasible due to small patient numbers and unmatched baseline characteristics. Trial registration NCT02601313 and NCT05041309.
Source: Journal of Hematology & Oncology
Authors: Javier Muñoz, Frederick L. Locke, Patrick M. Reagan, Andre Goy, Caron A. Jacobson, Brian T. Hill, John M. Timmerman, Ian W. Flinn, David B. Miklos, John M. Pagel, Marie José Kersten, Edouard Forcade, Max S. Topp, Roch Houot, Amer Beitinjaneh, Dan Zheng, Mengru Chang, Wangshu Zhang, Rhine R. Shen, Rita Damico Khalid, Ioana Kloos, Michael L. Wang
Institutions: Mayo Clinic Hospital, Banner MD Anderson Cancer Center, Moffitt Cancer Center, University of Rochester Medicine, University of Rochester, Hackensack University Medical Center, Dana-Farber Cancer Institute, Cleveland Clinic, University of California, Los Angeles, Tennessee Oncology, Stanford University, Amsterdam University Medical Centers, Cancer Center Amsterdam, University of Amsterdam, Centre Hospitalier Universitaire de Bordeaux, Universitätsklinikum Würzburg, Inserm, Centre Hospitalier Universitaire de Rennes, University of Miami, Kite (United States), The University of Texas MD Anderson Cancer Center
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,990
OpenAlex ID: W7155684078