Journal Article

Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma

Chaganti, Sridhar, Yang, Yin, Kersten, Marie José, Riedell, Peter A., Perales, Miguel-Angel, Cheng, Paul, Filosto, Simone, Farooq, Umar, Leslie, Lori A., Miklos, David B., Dorritie, Kathleen, Minnema, Monique C., To, Christina, Ulrickson, Matthew, Vardhanabhuti, Saran, Elsawy, Mahmoud, Reagan, Patrick M., Rapoport, Aaron P., Sureda, Anna, Song, Kevin W., Ghobadi, Armin, Schupp, Marco, Locke, Frederick L., Shahani, Shilpa A., Jacobson, Caron A., van Meerten, Tom, Oluwole, Olalekan O., McGuirk, Joseph, Westin, Jason R., Dickinson, Michael

2023

Overview

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. 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. 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. 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. (Funded by Kite; ZUMA-7 ClinicalTrials.gov number, NCT03391466.).

• Publisher: Massachusetts Medical Society
• Subject: Allergy / Antigens, CD19 - therapeutic use / Antineoplastic Agents, Immunological - therapeutic use / Autografts / B-cell lymphoma / Biological Products - therapeutic use / Bone Marrow Transplantation / CD19 antigen / Cell therapy / Chemotherapy / Chimeric antigen receptors / Design / Hematology / Humans / Immunology / Immunotherapy / Immunotherapy, Adoptive - adverse effects / Immunotherapy, Adoptive - methods / Leukemia / Lymphocytes B / Lymphocytes T / Lymphoma / Lymphoma, Large B-Cell, Diffuse - drug therapy / Oncology / Patients / Stem cell transplantation / Survival Analysis / T-Cells / Treatments in Oncology