Outcomes After Brexucabtagene Autoleucel Administered as a Standard Therapy for Adults With Relapsed/Refractory B-Cell ALL
Abstract
PURPOSE On the basis of the results of the ZUMA-3 trial, brexucabtagene autoleucel (brexu-cel), a CD19-directed chimeric antigen receptor T-cell therapy, gained US Food and Drug Administration approval in October 2021 for adults with relapsed/refractory (R/R) B-cell ALL (B-ALL). We report outcomes of patients treated with brexu-cel as a standard therapy. METHODS We developed a collaboration across 31 US centers to study adults with B-ALL who received brexu-cel outside the context of a clinical trial. Data were collected retrospectively from October 2021 to October 2023. Toxicities were graded per American Society for Transplantation and Cellular Therapy guidelines for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). RESULTS At the time of data lock, 204 patients had undergone apheresis and 189 were infused. Median follow-up time was 11.4 months. Forty-two percent of patients received brexu-cel in morphologic remission and would have been ineligible for participation in ZUMA-3. After brexu-cel, 151 achieved complete remission (CR), of which 79% were measurable residual disease (MRD) negative remissions. Median progression-free survival (PFS) was 9.5 months and median overall survival was not reached. Grade 3-4 CRS or ICANS occurred in 11% and 31%, respectively. In multivariable analysis, patients receiving consolidative hematopoietic cell transplantation (HCT; hazard ratio, 0.34 [95% CI, 0.14 to 0.85]) after brexu-cel had superior PFS compared with those who did not receive any consolidation or maintenance therapy. CONCLUSION Similar to ZUMA-3, high rates of MRD-negative CR were observed after brexu-cel treatment for R/R B-ALL. The use of HCT as consolidation after brexu-cel resulted in improved PFS.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (65)
Gregory W. Roloff
3Section of Hematology/Oncology, University of Chicago, Chicago, IL
Ibrahim Aldoss
Noam E. Kopmar
17Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA
Chenyu Lin
Department of Earth and Planetary Sciences, Harvard University
Simone E. Dekker
Division of Medical Oncology, Clinical Research Division, University of Washington/Fred Hutchinson Cancer Center, Seattle, WA
Vishal K. Gupta
Division of Hematology & Oncology, University of California Los Angeles, Los Angeles, CA
Timothy E. O'Connor
Division of Hematology/Oncology, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL
Nikeshan Jeyakumar
1University of California, Los Angeles, Los Angeles, United States
Ibrahim N. Muhsen
Section of Hematology and Oncology, Department of Medicine, Baylor College of Medicine, Houston, TX
Yannis Valtis
5Memorial Sloan Kettering Cancer Center, New York City, United States
Naveed Ahmed
Amy Zhang
Katharine Miller
3Quantitative Sciences Unit, Stanford University School of Medicine, Palo Alto, CA
Kaitlyn C. Dykes
10Division of Blood and Marrow Transplantation, University of California, San Diego, La Jolla, CA
Mohamed Ahmed
Evan C. Chen
15Adult Leukemia Program, Dana-Farber Cancer Institute, Boston, MA
Santiago Mercadal
Transplant and Cellular Therapy Program, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Marc Schwartz
Sean I. Tracy
1Center for Immunology, University of Minnesota, Minneapolis, MN
Bhagirathbhai Dholaria
Akash Mukherjee
2Oncology Hematology Care, Inc., Cincinnati, United States
Minoo Battiwalla
19Sarah Cannon Transplant and Cellular Therapy Program at TriStar Centennial Medical Center, HCA Healthcare, Nashville, TN
Aaron C. Logan
19Department of Medicine, University of California San Francisco, San Francisco, CA
Abdullah Ladha
2University of Southern California, Keck School of Medicine, Los Angeles, United States
Caitlin Guzowski
25Northside Hospital Cancer Institute, Atlanta, GA
Rasmus T. Hoeg
34Division of Malignant Hematology/Cellular Therapy and Transplantation, Department of Internal Medicine, University of California Davis, Sacramento, CA
Talal Hilal
13Mayo Clinic, Phoenix, AZ
Jozal Moore
45Division of Hematology and Oncology, Department of Medicine, Wilmot Cancer Institute of University of Rochester, Rochester, NY
Matthew P. Connor
Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA
LaQuisa C. Hill
14Baylor College of Medicine, Houston, TX
Stephanie B. Tsai
27Loyola University Medical Center, Maywood, IL
Joshua P. Sasine
24Cedars-Sinai Medical Center, Los Angeles, CA
Melhem M. Solh
26The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA
Vamsi K. Kota
16Georgia Cancer Center at Augusta University, Augusta, GA
Divya Koura
6University of California San Diego Moores Cancer Center, San Diego, CA
Muthu Veeraputhiran
University of Arkansas Medical Center, Little Rock, AK
Jessica T. Leonard
33Division of Hematology Oncology, Oregon Health & Science University, Portland, OR
Noelle V. Frey
Cell Therapy and Transplant Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia
Jae H. Park
Marlise R. Luskin
20Dana-Farber Cancer Institute, Boston, MA
Veronika Bachanova
Ahmed Galal
Vinod Pullarkat
1City of Hope, Duarte, United States
Wendy Stock
Ryan D. Cassaday
8Division of Hematology and Oncology, University of Washington, Seattle, WA
Bijal D. Shah
34Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL
Rawan Faramand
24Moffitt Cancer Center and Research Institute, Tampa, FL
Lori Muffly
1Division of Blood and Marrow Transplantation & Cellular Therapy, Stanford University, Stanford, CA
Caspian Oliai
George Yaghmour
University of Southern California, Los Angeles, California, United States
Katherine Sutherland
6Stanford University School of Medicine, Palo Alto, United States
Hector Zambrano
Danielle Bradshaw
Michal Kubiak
Navneet Majhail
26Sarah Cannon Cancer Network, Nashville, United States
Luke Mountjoy
28Sarah Cannon Transplant and Cellular Therapy Program at Colorado Blood Cancer Institute, Denver, United States
Shahbaz A. Malik
St David's South Austin Medical Center, Austin, TX
John Mathews
31Sarah Cannon Transplant and Cellular Therapy Program at Texas Oncology, Dallas, United States
Paul Shaughnessy
30Sarah Cannon Transplant and Cellular Therapy Program at Methodist Hospital, San Antonio, United States
Anjali S. Advani
Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, United States
Maryann Stefan
Kristen M. O'Dwyer
21University of Rochester Medical Center, Rochester, NY
Catherine J. Lee
13Fred Hutchinson Cancer Center, University of Washington, Seattle, WA
Betsy Blunk
Michael R. Bishop