Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma

TY - JOUR

T1 - Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma

AU - Locke, Frederick L

AU - Miklos, David B

AU - Jacobson, Caron A

AU - Perales, Miguel-Angel

AU - Kersten, Marie-José

AU - Oluwole, Olalekan O

AU - Ghobadi, Armin

AU - Rapoport, Aaron P

AU - McGuirk, Joseph

AU - Pagel, John M

AU - Muñoz, Javier

AU - Farooq, Umar

AU - van Meerten, Tom

AU - Reagan, Patrick M

AU - Sureda, Anna

AU - Flinn, Ian W

AU - Vandenberghe, Peter

AU - Song, Kevin W

AU - Dickinson, Michael

AU - Minnema, Monique C

AU - Riedell, Peter A

AU - Leslie, Lori A

AU - Chaganti, Sridhar

AU - Yang, Yin

AU - Filosto, Simone

AU - Shah, Jina

AU - Schupp, Marco

AU - To, Christina

AU - Cheng, Paul

AU - Gordon, Leo I

AU - Westin, Jason R

AU - All ZUMA-7 Investigators and Contributing Kite Members

AU - Kroger, Nicolaus

N1 - Copyright © 2021 Massachusetts Medical Society.

PY - 2022/2/17

Y1 - 2022/2/17

N2 - BACKGROUND: The prognosis of patients with early relapsed or refractory large B-cell lymphoma after the receipt of first-line chemoimmunotherapy is poor.METHODS: In this international, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with large B-cell lymphoma that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy to receive axicabtagene ciloleucel (axi-cel, an autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, followed by high-dose chemotherapy with autologous stem-cell transplantation in patients with a response to the chemoimmunotherapy). The primary end point was event-free survival according to blinded central review. Key secondary end points were response and overall survival. Safety was also assessed.RESULTS: A total of 180 patients were randomly assigned to receive axi-cel and 179 to receive standard care. The primary end-point analysis of event-free survival showed that axi-cel therapy was superior to standard care. At a median follow-up of 24.9 months, the median event-free survival was 8.3 months in the axi-cel group and 2.0 months in the standard-care group, and the 24-month event-free survival was 41% and 16%, respectively (hazard ratio for event or death, 0.40; 95% confidence interval, 0.31 to 0.51; P<0.001). A response occurred in 83% of the patients in the axi-cel group and in 50% of those in the standard-care group (with a complete response in 65% and 32%, respectively). In an interim analysis, the estimated overall survival at 2 years was 61% in the axi-cel group and 52% in the standard-care group. Adverse events of grade 3 or higher occurred in 91% of the patients who received axi-cel and in 83% of those who received standard care. Among patients who received axi-cel, grade 3 or higher cytokine release syndrome occurred in 6% and grade 3 or higher neurologic events in 21%. No deaths related to cytokine release syndrome or neurologic events occurred.CONCLUSIONS: Axi-cel therapy led to significant improvements, as compared with standard care, in event-free survival and response, with the expected level of high-grade toxic effects. (Funded by Kite; ZUMA-7 ClinicalTrials.gov number, NCT03391466.).

AB - BACKGROUND: The prognosis of patients with early relapsed or refractory large B-cell lymphoma after the receipt of first-line chemoimmunotherapy is poor.METHODS: In this international, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with large B-cell lymphoma that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy to receive axicabtagene ciloleucel (axi-cel, an autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, followed by high-dose chemotherapy with autologous stem-cell transplantation in patients with a response to the chemoimmunotherapy). The primary end point was event-free survival according to blinded central review. Key secondary end points were response and overall survival. Safety was also assessed.RESULTS: A total of 180 patients were randomly assigned to receive axi-cel and 179 to receive standard care. The primary end-point analysis of event-free survival showed that axi-cel therapy was superior to standard care. At a median follow-up of 24.9 months, the median event-free survival was 8.3 months in the axi-cel group and 2.0 months in the standard-care group, and the 24-month event-free survival was 41% and 16%, respectively (hazard ratio for event or death, 0.40; 95% confidence interval, 0.31 to 0.51; P<0.001). A response occurred in 83% of the patients in the axi-cel group and in 50% of those in the standard-care group (with a complete response in 65% and 32%, respectively). In an interim analysis, the estimated overall survival at 2 years was 61% in the axi-cel group and 52% in the standard-care group. Adverse events of grade 3 or higher occurred in 91% of the patients who received axi-cel and in 83% of those who received standard care. Among patients who received axi-cel, grade 3 or higher cytokine release syndrome occurred in 6% and grade 3 or higher neurologic events in 21%. No deaths related to cytokine release syndrome or neurologic events occurred.CONCLUSIONS: Axi-cel therapy led to significant improvements, as compared with standard care, in event-free survival and response, with the expected level of high-grade toxic effects. (Funded by Kite; ZUMA-7 ClinicalTrials.gov number, NCT03391466.).

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Agents, Immunological/adverse effects

KW - Biological Products/adverse effects

KW - Drug Resistance, Neoplasm

KW - Female

KW - Humans

KW - Immunotherapy, Adoptive

KW - Lymphoma, Large B-Cell, Diffuse/drug therapy

KW - Male

KW - Middle Aged

KW - Progression-Free Survival

KW - Receptors, Chimeric Antigen/antagonists & inhibitors

KW - Stem Cell Transplantation

KW - Transplantation, Autologous

U2 - 10.1056/NEJMoa2116133

DO - 10.1056/NEJMoa2116133

M3 - SCORING: Journal article

C2 - 34891224

VL - 386

SP - 640

EP - 654

JO - NEW ENGL J MED

JF - NEW ENGL J MED

SN - 0028-4793

IS - 7

ER -