Brexucabtagene autoleucel for BTKi-naive relapsed/refractory mantle cell lymphoma: primary analysis of ZUMA-2 cohort 3

Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for adults with relapsed/refractory (R/R) mantle cell lymphoma (MCL) based on the ZUMA-2 cohort 1 (ClinicalTrials.gov identifier: NCT02601313) study in which brexu-cel demonstrated a 93% objective response rate (ORR) and 67% complete response (CR) rate in patients with R/R MCL and previous BTKi therapy (N = 60). Here, we report the primary results of ZUMA-2 cohort 3 (brexu-cel in patients with BTKi-naive R/R MCL). Adults received brexu-cel at 2 × 106 anti-CD19 CAR T cells per kilogram. The primary end point was ORR assessed by independent radiology review committee (IRRC). As of 26 November 2023, 95 patients were enrolled, and 86 received brexu-cel; median follow-up was 15.5 months. The primary end point was met, with a 91% ORR (95% confidence interval [CI], 82.5-95.9; P< .0001; N = 86) and a CR rate of 73% (95% CI, 62.6-82.2). Estimated 12-month progression-free survival (PFS), duration of response, and overall survival (OS) rates were 75%, 80%, and 90%, respectively. Among 95 enrolled patients, the ORR was 82%, the CR rate was 66%, and the 12-month PFS and OS rates (95% CI) were 73% (62.1-80.8) and 85% (75.6-90.7), respectively. Most patients (88%) experienced treatment-related grade ≥3 adverse events, including 4 treatment-related grade 5 events. Consistent with cohort 1, brexu-cel demonstrated a high ORR and similar safety profile. These results support the continued use of brexu-cel in patients with R/R MCL, and consideration in some patients without previous BTKi therapy who have high-risk disease. This trial was registered at clinicaltrials.gov as #NCT04880434.

Authors

Institutions

Publication Details

Journal
Blood
Published
2025-10-29
DOI
https://doi.org/10.1182/blood.2025029734
Citations
3
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
3.14
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Brexucabtagene autoleucel for BTKi-naive relapsed/refractory mantle cell lymphoma: primary analysis of ZUMA-2 cohort 3

Brian T. Hill, Georg Heß, Wen‐Kai Weng, Ioana Kloos et al.
3 citations
Blood
CAR-T cell therapy research
3.14
article

Brexucabtagene autoleucel for BTKi-naive relapsed/refractory mantle cell lymphoma: primary analysis of ZUMA-2 cohort 3

Brian T. Hill, Georg Heß, Wen‐Kai Weng, Ioana Kloos, Pim G. N. J. Mutsaers, Roch Houot, Ahmed M. Galal, Krish Patel, Marie José Kersten, Gloria Iacoboni, Alejandro Martı́n, Tom van Meerten, Charles Herbaux, Justyna Kanska, Martin H. Dreyling, Eva Giné, Patrick M. Reagan, Rhine R. Shen, Robin Sanderson, Édouard Forcade, André Goy, Max S. Topp, Michael L. Wang, Wangshu Zhang, Dan Zheng, Rita Damico Khalid
article en
3 citations

Abstract

Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for adults with relapsed/refractory (R/R) mantle cell lymphoma (MCL) based on the ZUMA-2 cohort 1 (ClinicalTrials.gov identifier: NCT02601313) study in which brexu-cel demonstrated a 93% objective response rate (ORR) and 67% complete response (CR) rate in patients with R/R MCL and previous BTKi therapy (N = 60). Here, we report the primary results of ZUMA-2 cohort 3 (brexu-cel in patients with BTKi-naive R/R MCL). Adults received brexu-cel at 2 × 106 anti-CD19 CAR T cells per kilogram. The primary end point was ORR assessed by independent radiology review committee (IRRC). As of 26 November 2023, 95 patients were enrolled, and 86 received brexu-cel; median follow-up was 15.5 months. The primary end point was met, with a 91% ORR (95% confidence interval [CI], 82.5-95.9; P< .0001; N = 86) and a CR rate of 73% (95% CI, 62.6-82.2). Estimated 12-month progression-free survival (PFS), duration of response, and overall survival (OS) rates were 75%, 80%, and 90%, respectively. Among 95 enrolled patients, the ORR was 82%, the CR rate was 66%, and the 12-month PFS and OS rates (95% CI) were 73% (62.1-80.8) and 85% (75.6-90.7), respectively. Most patients (88%) experienced treatment-related grade ≥3 adverse events, including 4 treatment-related grade 5 events. Consistent with cohort 1, brexu-cel demonstrated a high ORR and similar safety profile. These results support the continued use of brexu-cel in patients with R/R MCL, and consideration in some patients without previous BTKi therapy who have high-risk disease. This trial was registered at clinicaltrials.gov as #NCT04880434.

BloodVol. 147(12)
Cleveland Clinic (US), Hackensack University Medical Center (US), University Medical Center Groningen (NL), The University of Texas MD Anderson Cancer Center (US), Inserm (FR), Palo Alto University (US), Universidad de Salamanca (ES), Johannes Gutenberg University Mainz (DE), Rabbinical College of America (US), Erasmus MC (NL), Health Net (US), University of Rochester Medical Center (US), Centre Hospitalier Universitaire de Bordeaux (FR), LMU Klinikum (DE), Centre Hospitalier Universitaire de Montpellier (FR), University Medical Center of the Johannes Gutenberg University Mainz (DE), Complejo Hospitalario de Salamanca (ES), Sarah Cannon (US), Klinik und Poliklinik für Nuklearmedizin (DE), Hospital Clínic de Barcelona (ES), Universitätsklinikum Würzburg (DE), Vall d'Hebron Hospital Universitari (ES), Instituto de Investigación Biomédica de Salamanca (ES), Gilead Sciences (Australia) (AU), Kite (United States) (US), Institut Universitaire de Recherche Clinique (FR), Amsterdam University Medical Centers (NL), King's College Hospital (GB), Centre Hospitalier Universitaire de Rennes (FR), Institut de Biologie Moléculaire et Cellulaire (FR), Centro de Investigación Biomédica en Red de Cáncer (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Vall d'Hebron Institute of Oncology (ES), Atlantic Health System (US), Ludwig-Maximilians-Universität München (DE), University of Amsterdam (NL), Stanford University (US)
Openalex Percentile: Top 7%
CAR-T cell therapy research
3.14
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.