Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma
- Author(s)
- Locke, FL; Miklos, DB; Jacobson, CA; Perales, MA; Kersten, MJ; Oluwole, OO; Ghobadi, A; Rapoport, AP; McGuirk, J; Pagel, JM; Munoz, J; Farooq, U; van Meerten, T; Reagan, PM; Sureda, A; Flinn, IW; Vandenberghe, P; Song, KW; Dickinson, M; Minnema, MC; Riedell, PA; Leslie, LA; Chaganti, S; Yang, Y; Filosto, S; Shah, J; Schupp, M; To, C; Cheng, P; Gordon, LI; Westin, JR; All ZUMA-7 Investigators; Contributing Kite Members;
- Details
- Publication Year 2022-02-17,Volume 386,Issue #7,Page 640-654
- Journal Title
- New England Journal of Medicine
- Publication Type
- Research article
- Abstract
- 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.).
- Keywords
- Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological/adverse effects/*therapeutic use; Biological Products/adverse effects/*therapeutic use; Drug Resistance, Neoplasm; Female; Humans; *Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse/*drug therapy; Male; Middle Aged; Progression-Free Survival; Receptors, Chimeric Antigen/*antagonists & inhibitors; Stem Cell Transplantation; Transplantation, Autologous
- Department(s)
- Haematology
- PubMed ID
- 34891224
- Publisher's Version
- https://doi.org/10.1056/NEJMoa2116133
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- Refer to copyright notice on published article.
Creation Date: 2025-01-24 05:57:01
Last Modified: 2025-01-24 05:58:22