Axi-Cel Extends Survival vs Standard of Care for R/R LBCL

Data from the phase 3 ZUMA-7 trial of axicabtagene ciloleucel (axi-cel) in patients with early relapsed or refractory (R/R) large B-cell lymphoma (LBCL) demonstrate improved overall survival (OS) compared with the standard of care. The findings were published in New England Journal of Medicine and featured in a late-breaking abstract at the 2023 American Society of Clinical Oncology Annual Meeting.

“This is the first time that, in the curative intent setting in second line, there has been improvement in overall survival for nearly 30 years. So we're pretty excited about that finding,” lead author Jason Westin, MD, MS, FACP, director of the Lymphoma Clinical Research Program at Texas MD Anderson Cancer Center, told The American Journal of Managed Care^® in an interview.

The ZUMA-7 trial included 359 patients with LBCL that was refractory to first-line therapy or relapsed within 12 months of first-line chemoimmunotherapy. Patients were randomized 1:1 to receive either axi-cel (n = 180) or standard-of-care treatment (n = 179) with a primary end point of event-free survival (EFS). In the EFS analysis, axi-cel showed superiority to the standard of care, with a median EFS of 8.3 months vs 2.0 months in the standard-of-care cohort at a median follow-up of 24.9 months.

The prespecified OS analysis was conducted 5 years after the first patient underwent randomization. At a median follow-up of 47.2 months, 82 patients and 95 patients had died in the axi-cel and standard-of-care arms, respectively.

In the axi-cel cohort, median OS was not reached, whereas the standard-of-care cohort had a median OS of 31.1 months. Estimated 4-year OS was 54.6% in patients who received axi-cel and 46.0% in the standard-of-care group (HR for death, 0.73; 95% CI, 0.54-0.98; P = .03). Median progression-free survival (PFS) was 14.7 months among patients treated with axi-cel and 3.7 months in the standard-of-care cohort. The estimated 4-year rates of PFS were 41.8% in the axi-cel group and 24.45 in the standard-of-care group (HR, 0.51; 95% CI, 0.38-0.67.

Longer OS was seen in the intention-to-treat population, which included 74% of patients in the overall population who had primary refractory disease and other high-risk disease characteristics. Investigators noted there were no new treatment-related deaths in the time since the primary EFS analysis.

The authors noted several limitations, including a higher proportion of non-Hispanic White patients vs other racial or ethnic groups. This may reflect issue of care access and a lack of racial and ethnic diversity in clinical trials in general.

“Although favorable outcomes have been observed with axi-cel treatment regardless of race or ethnicity, interventions that are aimed at increasing the enrollment of diverse racial and ethnic groups in trials should be encouraged,” they wrote.

The trial also included a narrower patient pool than real-world settings, although the authors noted that real-world studies of axi-cel have demonstrated the therapy’s efficacy in broader populations.

“On our trial, we showed definitively that CAR T-cell [therapy] in the second line is the preferred approach, because on the standard of care on ZUMA-7, more than half of the patients did not respond to chemo and went on to get a subsequent cellular immunotherapy—57% did that and still had a significant improvement in overall survival,” Westin said. “So effectively, saving CAR T cell for later is an inferior approach, and axi-cel should be a second-line treatment option.”

Reference

Westin JR, Oluwole OO, Kersten MJ, et al. Survival with axicabtagene ciloleucel in large B-cell lymphoma. N Engl J Med. 2023;389(2):148-157. doi:10.1056/NEJMoa2301665