Outcomes of brexucabtagene autoleucel in patients with relapsed/refractory acute lymphoblastic leukemia with CNS involvement

Patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system (CNS) involvement (CNS B-ALL) have poor outcomes and were frequently excluded from CD19-targeting chimeric antigen receptor (CAR) T-cell clinical trials. The efficacy and safety of brexucabtagene autoleucel (brexu-cel) in adults with R/R B-ALL was established by the ZUMA-3 trial, which excluded patients with advanced or symptomatic CNS involvement. In this retrospective multicenter analysis, we investigated the safety and efficacy of brexu-cel in patients with CNS B-ALL using data from the ROCCA (Real-World Outcomes Collaborative for CAR T in ALL) consortium. Of 189 patients who received infusion, 31 had CNS-2 (presence of blasts in cerebrospinal fluid with <5 white blood cells [WBCs] per μL) or CNS-3 (presence of blasts with >5 WBCs per μL and/or clinical signs/symptoms) disease before apheresis and are the focus of this report. The median age was 46.5 years (range, 24-76), and 58.1% were male. Most (87.1%) received bridging therapy. After brexu-cel, 21 of 24 patients with CNS restaging (87.5%) achieved CNS-1. Additionally, 28 of 30 evaluable patients achieved marrow complete remission; 25 were measurable residual disease negative. No statistically significant differences were seen in progression-free survival or overall survival after brexu-cel among patients with or without CNS involvement. Similarly, grade 3/4 immune effector cell-associated neurotoxicity syndrome occurred similarly in patients with (35.5%) and without (30%) CNS disease. In conclusion, our data suggest that brexu-cel results in high response rates in patients with CNS B-ALL, with toxicity comparable with that in patients without CNS involvement.

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Publication Details

Journal
Blood Advances
Published
2025-05-07
DOI
https://doi.org/10.1182/bloodadvances.2024015779
Citations
2
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
2.09

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article

Outcomes of brexucabtagene autoleucel in patients with relapsed/refractory acute lymphoblastic leukemia with CNS involvement

Lori S. Muffly, Melhem Solh, Rawan Faramand, Joshua Sasine et al.
2 citations
Blood Advances
CAR-T cell therapy research
2.09
article

Outcomes of brexucabtagene autoleucel in patients with relapsed/refractory acute lymphoblastic leukemia with CNS involvement

Lori S. Muffly, Melhem Solh, Rawan Faramand, Joshua Sasine, Catherine J. Lee, Simone E. Dekker, Paul Shaughnessy, Santiago Mercadal, Navneet S. Majhail, Divya Koura, Matthew P. Connor, Bijal Shah, Marc S. Schwartz, Luke Mountjoy, Caspian Oliai, Jessica Leonard, Tamer Adel Othman, Ibrahim Taha Aldoss, Gregory W. Roloff, Noam E. Kopmar, LaQuisa C. Hill, Ibrahim N. Muhsen, Muthu Sendhil Kumaran, Caitlin Guzowski, Sang‐Bing Tsai, Aaron C. Logan, Ryan D. Cassaday, Minoo Battiwalla, Kaitlyn C. Dykes, John A. Mathews, Yannis K. Valtis, Noelle V. Frey, Timothy E. O’Connor, Nikeshan Jeyakumar, Vishal Gupta, Amy Zhang, Mohamed Ahmed, Jae H. Park, Shahbaz A. Malik, Katherine C. Sutherland, Katharine Miller
article en
2 citations

Abstract

Patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system (CNS) involvement (CNS B-ALL) have poor outcomes and were frequently excluded from CD19-targeting chimeric antigen receptor (CAR) T-cell clinical trials. The efficacy and safety of brexucabtagene autoleucel (brexu-cel) in adults with R/R B-ALL was established by the ZUMA-3 trial, which excluded patients with advanced or symptomatic CNS involvement. In this retrospective multicenter analysis, we investigated the safety and efficacy of brexu-cel in patients with CNS B-ALL using data from the ROCCA (Real-World Outcomes Collaborative for CAR T in ALL) consortium. Of 189 patients who received infusion, 31 had CNS-2 (presence of blasts in cerebrospinal fluid with <5 white blood cells [WBCs] per μL) or CNS-3 (presence of blasts with >5 WBCs per μL and/or clinical signs/symptoms) disease before apheresis and are the focus of this report. The median age was 46.5 years (range, 24-76), and 58.1% were male. Most (87.1%) received bridging therapy. After brexu-cel, 21 of 24 patients with CNS restaging (87.5%) achieved CNS-1. Additionally, 28 of 30 evaluable patients achieved marrow complete remission; 25 were measurable residual disease negative. No statistically significant differences were seen in progression-free survival or overall survival after brexu-cel among patients with or without CNS involvement. Similarly, grade 3/4 immune effector cell-associated neurotoxicity syndrome occurred similarly in patients with (35.5%) and without (30%) CNS disease. In conclusion, our data suggest that brexu-cel results in high response rates in patients with CNS B-ALL, with toxicity comparable with that in patients without CNS involvement.

Blood AdvancesVol. 9(16)
Northside Hospital (US), Cedars-Sinai Medical Center (US), Houston Methodist (US), City Of Hope National Medical Center (US), Loyola University Medical Center (US), Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), Memorial Sloan Kettering Cancer Center (US), University of California, Los Angeles (US), Oregon Health & Science University (US), Palo Alto University (US), University of California, San Francisco (US), Baylor College of Medicine (US), University of Washington (US), University of Utah (US), University of Arkansas Medical Center (US), UCLA Health (US), Hospital of the University of Pennsylvania (US), Texas Oncology (US), Huntsman Cancer Institute (US), Moffitt Cancer Center (US), University of California San Diego (US), University of Chicago (US), Fred Hutch Cancer Center (US), Blood Systems Research Institute (US), Sarah Cannon (US), Methodist Hospital (US), City of Hope (US), Methodist Hospital (US), CHRISTUS Transplant Institute (US), Colorado Blood Cancer Institute (US), University of Colorado Cancer Center (US), University of Colorado Anschutz Medical Campus (US), University of Pennsylvania (US), University of Arkansas for Medical Sciences (US), University of Colorado Denver (US), Stanford University (US)
Amgen, Bristol-Myers Squibb, Pfizer, AstraZeneca, Sanofi, Gilead Sciences, Celgene, Moffitt Cancer Center, Vanda Pharmaceuticals, Jazz Pharmaceuticals, Adaptive Biotechnologies, BeiGene, Incyte, Seagen, Astellas Pharma, Servier, Pharmacyclics
Good health and well-being
Openalex Percentile: Top 12%
CAR-T cell therapy research
2.09
DOIOpen Access PDFOpenAlex
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