Researchers recently presented the results of the primary overall survival (OS) analysis in the ZUMA-7 clinical trial at the 2023 ASCO Annual Meeting in Chicago, IL. Jason Westin, MD, University of Texas MD Anderson Cancer Center, Houston, TX, and colleagues examined the OS of patients with early relapsed or refractory large B-cell lymphoma (R/R LBCL) who received axicabtagene ciloleucel (axi-cel) vs standard of care (SOC) for second-line therapy.

Starting January 2018, researchers randomized 359 patients in the ZUMA-7 trial in a 1:1 ratio to receive axi-cel (180 patients) or SOC (179 patients) as second-line therapy. Per protocol, Dr Westin and colleagues completed the intention-to-treat primary OS analysis 5 years after the first patient was enrolled. They used a log-rank test with randomization stratification factors to compare the OS of the two patient groups and performed prespecified sensitivity analyses using the Rank-Preserving Structural Failed Time (RPSFT) and Inverse Probability of Censoring Weights (IPCW) models to account for SOC-treated patients who may have received additional treatment with cellular immunotherapy off protocol.

The researchers found that 47.2 months post-treatment, patients treated with axi-cel showed a statistically significant improvement in OS (hazard ratio [HR], 0.726; 95% confidence interval [95% CI], 0.540-0.977); stratified log-rank 1-sided P = .0168 [efficacy boundary, 0.0249]) and longer median OS (not reached) compared to patients treated with SOC (31.1 months). During the follow-up period, OS estimates for the axi-cel arm were higher at 54.6% vs the SOC arm, which was 46%. The OS benefit was also demonstrated in an analysis of prespecified subgroups, which included patients ≥65 years old, early relapse, and high-grade B-cell lymphoma.

Of the patients who were treated with SOC, 57% (102) received additional cellular immunotherapy off protocol. The sensitivity analyses performed to account for any confounding effect from a switch in treatment found that there was a substantial OS benefit with axi-cel treatment compared to SOC (RPSFT: stratified HR, 0.608; 95% CI, 0.449-0.824. IPCW: stratified HR, 0.633; 95% CI, 0.409-0.981). In addition, patients treated with axi-cel had higher 48-month progression-free survival estimates (41.8%) than those treated with SOC (24.4%).

The OS benefit of axi-cel was accompanied by a consistent safety profile when compared to previous studies. Since the early feasibility study in ZUMA-7, patients did not experience new neurologic events and did not develop new cytokine release syndrome, and no new treatment-related deaths occurred.

Overall, Dr Westin and colleagues found that the use of “axi-cel as second-line therapy demonstrated a significant improvement in overall survival over historical standard of care in patients with early relapsed/refractory LBCL.”

Westin J, Oluwole OO, Kersten MJ, et al. Primary overall survival analysis of the phase 3 randomized ZUMA‑7 study of axicabtagene ciloleucel versus standard‑of‑care therapy in relapsed/refractory large B-cell lymphoma. Presented at: the 2023 ASCO Annual Meeting; June 2-6, 2023; Chicago, IL, and virtual; Abstract LBA107.