TY - JOUR
T1 - Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma
AU - Locke, Frederick L
AU - Miklos, David B
AU - All ZUMA-7 Investigators and Contributing Kite Members
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 - Lugtenburg, Elly
N1 - Funding Information:
Supported by Kite, a Gilead company .
Publisher 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.).
UR - http://www.scopus.com/inward/record.url?scp=85122373111&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2116133
DO - 10.1056/NEJMoa2116133
M3 - Article
C2 - 34891224
SN - 0028-4793
VL - 386
SP - 640
EP - 654
JO - The New England journal of medicine
JF - The New England journal of medicine
IS - 7
ER -