TY - JOUR
T1 - Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma
AU - ZUMA-7 Investigators and Kite Members
AU - Westin, Jason R.
AU - Oluwole, Olalekan O.
AU - Kersten, Marie José
AU - Miklos, David B.
AU - Perales, Miguel-Angel
AU - Ghobadi, Armin
AU - Rapoport, Aaron P.
AU - Sureda, Anna
AU - Jacobson, Caron A.
AU - Farooq, Umar
AU - van Meerten, Tom
AU - Ulrickson, Matthew
AU - Elsawy, Mahmoud
AU - Leslie, Lori A.
AU - Chaganti, Sridhar
AU - Dickinson, Michael
AU - Dorritie, Kathleen
AU - Reagan, Patrick M.
AU - McGuirk, Joseph
AU - Song, Kevin W.
AU - Riedell, Peter A.
AU - Minnema, Monique C.
AU - Yang, Yin
AU - Vardhanabhuti, Saran
AU - Filosto, Simone
AU - Cheng, Paul
AU - Shahani, Shilpa A.
AU - Schupp, Marco
AU - To, Christina
AU - Locke, Frederick L.
N1 - Funding Information: The trial was conducted in accordance with the principles of the Declaration of Helsinki and was funded by Kite. The protocol was approved by the institutional review board at each participating institution. All the patients provided written informed consent. The authors collaborated on trial design and data collection, analysis, and interpretation of the results. The first draft of the manuscript was written by the first and last authors with sponsor-funded medical writing support. All the authors contributed to the writing of the manuscript and vouch for the accuracy and completeness of the data and for the fidelity of the trial to the protocol. The authors were under a confidentiality agreement with the sponsor and had data access. The sponsor participated in the assessment of the data. Funding Information: Supported by Kite . Publisher Copyright: © 2023 Massachusetts Medical Society.
PY - 2023/7/13
Y1 - 2023/7/13
N2 - Background: In an analysis of the primary outcome of this phase 3 trial, patients with early relapsed or refractory large B-cell lymphoma who received axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, as second-line treatment had significantly longer event-free survival than those who received standard care. Data were needed on longer-term outcomes. Methods: In this trial, we randomly assigned patients with early relapsed or refractory large B-cell lymphoma in a 1:1 ratio to receive either axi-cel or standard care (two to three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation in patients who had a response). The primary outcome was event-free survival, and key secondary outcomes were response and overall survival. Here, we report the results of the prespecified overall survival analysis at 5 years after the first patient underwent randomization. Results: A total of 359 patients underwent randomization to receive axi-cel (180 patients) or standard care (179 patients). At a median follow-up of 47.2 months, death had been reported in 82 patients in the axi-cel group and in 95 patients in the standard-care group. The median overall survival was not reached in the axi-cel group and was 31.1 months in the standard-care group; the estimated 4-year overall survival was 54.6% and 46.0%, respectively (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.54 to 0.98; P=0.03 by stratified two-sided log-rank test). This increased survival with axi-cel was observed in the intention-to-treat population, which included 74% of patients with primary refractory disease and other high-risk features. The median investigator-assessed progression-free survival was 14.7 months in the axi-cel group and 3.7 months in the standard-care group, with estimated 4-year percentages of 41.8% and 24.4%, respectively (hazard ratio, 0.51; 95% CI, 0.38 to 0.67). No new treatment-related deaths had occurred since the primary analysis of event-free survival. Conclusions: At a median follow-up of 47.2 months, axi-cel as second-line treatment for patients with early relapsed or refractory large B-cell lymphoma resulted in significantly longer overall survival than standard care.
AB - Background: In an analysis of the primary outcome of this phase 3 trial, patients with early relapsed or refractory large B-cell lymphoma who received axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, as second-line treatment had significantly longer event-free survival than those who received standard care. Data were needed on longer-term outcomes. Methods: In this trial, we randomly assigned patients with early relapsed or refractory large B-cell lymphoma in a 1:1 ratio to receive either axi-cel or standard care (two to three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation in patients who had a response). The primary outcome was event-free survival, and key secondary outcomes were response and overall survival. Here, we report the results of the prespecified overall survival analysis at 5 years after the first patient underwent randomization. Results: A total of 359 patients underwent randomization to receive axi-cel (180 patients) or standard care (179 patients). At a median follow-up of 47.2 months, death had been reported in 82 patients in the axi-cel group and in 95 patients in the standard-care group. The median overall survival was not reached in the axi-cel group and was 31.1 months in the standard-care group; the estimated 4-year overall survival was 54.6% and 46.0%, respectively (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.54 to 0.98; P=0.03 by stratified two-sided log-rank test). This increased survival with axi-cel was observed in the intention-to-treat population, which included 74% of patients with primary refractory disease and other high-risk features. The median investigator-assessed progression-free survival was 14.7 months in the axi-cel group and 3.7 months in the standard-care group, with estimated 4-year percentages of 41.8% and 24.4%, respectively (hazard ratio, 0.51; 95% CI, 0.38 to 0.67). No new treatment-related deaths had occurred since the primary analysis of event-free survival. Conclusions: At a median follow-up of 47.2 months, axi-cel as second-line treatment for patients with early relapsed or refractory large B-cell lymphoma resulted in significantly longer overall survival than standard care.
KW - Allergy/Immunology
KW - Bone Marrow Transplantation
KW - Hematology/Oncology
KW - Leukemia/Lymphoma
KW - T-Cells
KW - Treatments in Oncology
UR - http://www.scopus.com/inward/record.url?scp=85163124132&partnerID=8YFLogxK
U2 - https://doi.org/10.1056/NEJMoa2301665
DO - https://doi.org/10.1056/NEJMoa2301665
M3 - Article
C2 - 37272527
SN - 0028-4793
VL - 389
SP - 148
EP - 157
JO - The New England journal of medicine
JF - The New England journal of medicine
IS - 2
ER -