As reported in The New England Journal of Medicine by Jason R. Westin, MD, and colleagues, the overall survival analysis from the phase III ZUMA-7 trial showed significant benefit with axicabtagene ciloleucel vs standard care in patients with early relapsed or refractory large B-cell lymphoma. The study supported the April 2022 approval of axicabtagene ciloleucel in this setting on the basis of improved event-free survival.
Jason R. Westin, MD
Study Details
In the international trial, 359 patients refractory to first-line treatment or who relapsed within 12 months after first-line chemoimmunotherapy were randomly assigned between January 2018 and October 2019 to receive axicabtagene ciloleucel (n = 180) or standard care (n = 179). Standard care consisted of two or three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem cell transplantation in patients with response. The current analysis was a prespecified overall survival analysis at 5 years after the first patient underwent random assignment.
Key Findings
At a median follow-up of 47.2 months (range = 39.8–60.0 months), death had occurred in 82 patients in the axicabtagene ciloleucel group vs 95 patients in the standard-care group. Median overall survival was not reached (95% confidence interval [CI] = 28.6 months to not estimable) in the axicabtagene ciloleucel group vs 31.1 months (95% CI = 17.1 months to not estimable) in the standard-care group (hazard ratio [HR] = 0.73, 95% CI = 0.54–0.98, P = .03). Overall survival rate at 4 years was 54.6% (95% CI = 47.0%–61.6%) in the axicabtagene ciloleucel group vs 46.0% (95% CI = 38.4%–53.2%) in the standard-care group.
Median investigator-assessed progression-free survival was 14.7 months (95% CI = 5.4–43.5 months) in the axicabtagene ciloleucel group vs 3.7 months (95% CI = 2.9–5.3 months) in the standard-care group (HR = 0.51, 95% CI = 0.38–0.67). Progression-free survival rate at 4 years was 41.8% (95% CI = 34.1%–49.2%) vs 24.4% (95% CI = 17.2%–32.2%).
A total of 102 patients (57.0%) in the standard-care group received subsequent cellular immunotherapy after disease progression or lack of response; of these patients, 79 (77.5%) received axicabtagene ciloleucel. Prespecified sensitivity analyses assessing the confounding effect of treatment switching on overall survival in the standard-care group showed a greater overall survival benefit with axicabtagene ciloleucel vs standard care.
The investigators concluded: “At a median follow-up of 47.2 months, axicabtagene ciloleucel as second-line treatment for patients with early relapsed or refractory large B-cell lymphoma resulted in significantly longer overall survival than standard care.”
Dr. Westin, of The University of Texas MD Anderson Cancer Center, is the corresponding author of The New England Journal of Medicine article.
Disclosure: The study was funded by Kite. For full disclosures of the study authors, visit nejm.org.
