New Survival Data Cements Axi-Cel's Place as a Second-Line SOC for LBCL

Axicabtagene ciloleucel (axi-cel; Yescarta; Kite) chimeric antigen receptor (CAR) T-cell therapy significantly improved overall survival (OS) compared with standard of care (SOC) in patients with early relapsed/refractory large B-cell lymphoma (LBCL) in final data from the phase 3 ZUMA-7 clinical trial (NCT03391466).

The final survival analysis data were presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois, by Jason Westin, MD, director, lymphoma clinical research, and section chief, aggressive lymphoma research team, Unviersity of Texas MD Anderson Cancer Center.

“ZUMA-7...showed a significant improvement in event free survival (EFS) for axi-cel over SOC. Based upon the superior EFS, axi-cel was approved in second line for patients with relapsed LBCL in many countries,” Westin said during his presentation. “Here we present the final OS analysis in the ZUMA-7 trial.”

ZUMA-7 randomized 180 patients with LBCL to the axi-cel arm and 179 to the SOC arm. Of the total enrolled patients, 94% (n = 170) of the axi-cel arm received axi-cel while only 36% (n = 64) actually received the SOC of high-dose therapy (HDT) followed by autologous stem cell transplant (ASCT) after salvage chemotherapy, largely due to progressive disease. Over half (57%; n = 102) of patients in the SOC arm subsequently received cellular immunotherapy, including CAR T-cell therapy, off-protocol. Baseline characteristics were well-balanced and represented a high-risk disease population.

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Westin presented data from the OS analysis, sharing that at a median follow-up of 47.2 months, axi-cel treatment improved OS with a hazard ratio [HR] of 0.726 (95% CI, 0.540-0.977; one-sided P = .0168). Median OS was not reached in the axi-cel arm and was 31 months in the SOC arm, which is an improvement from historical studies of survival with SOC treatment, including the ORCHARRD study (NCT01014208), which yielded a 10-month median OS. Furthermore, the axi-cel arm had a 4-year OS rate of 54.6% compared with 46.0% in the SOC arm.The data representa 27.4% reduction in the risk of death, even with over half of SOC patients receiving subsequent cellular immunotherapy.

“This establishes that saving CAR T-cell therapy for third line treatment after lack of durable response to chemotherapy cannot match second line axi-cel treatment,” Westin commented on the data.

The survival benefit was seen across all assessed subgroups and the axi-cel arm had a similar benefit in progression-free survival( PFS) over the follow-up period, with an HR of 0.506 (95% CI, 0.383-0.669’ one-sided P < .0001). PFS was 14.7 months in the axi-cel arm and 3.7 months in the SOC arm and 4-year PFS rates were 41.8% and 24.4%, respectively. There were no changes in treatment-related serious or fatal adverse events since the primary EFS analysis of ZUMA-7.

“We believe our data representa paradigm shift. Axi-cel in second-line improves OS for patients with early relapsed LBCL versus the previous paradigm,” Westin said. “With a median follow-up of 47.2 months, these mature survival data are consistent with curative therapy,” Westin concluded. “To our knowledge, ZUMA-7 is the first randomized trial in any cancer to show an OS benefit for a CAR T-cell therapy over an existing SOC, and this is the first trial in nearly 30 years to significantly improve OS in the second line treatment for patients with LBCL receiving curative intent therapy. ZUMA-7 confirms axi-cel is a SOC...”

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REFERENCE

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