Axi-Cel Outperforms Standard Second-Line Treatment for LBCL

Second-line treatment with axicabtagene ciloleucel (axi-cel) can improve overall survival (OS) when compared to standard care in patients with relapsed or refractory large B-cell lymphoma (LBCL), according to phase 3 data presented at the ASCO Annual Meeting 2023.¹

These data, from the ZUMA-7 trial, showed a 27.4% reduction in the risk of death for patients who received the chimeric antigen receptor (CAR) T-cell therapy, despite 57% of patients in the standard care arm receiving subsequent cellular immunotherapy off protocol.

“ZUMA-7 confirms axi-cel is a second-line standard of care for patients with refractory or early relapsed large B-cell lymphoma based upon superior survival,” said study presenter Jason Westin, MD, of the University of Texas MD Anderson Cancer Center in Houston.

The ZUMA-7 trial (ClinicalTrials.gov Identifier: NCT03391466) included 359 patients with relapsed or refractory LBCL who had received no more than 12 months of first-line therapy and were intended to undergo high-dose therapy and autologous stem cell transplant (HDT-ASCT). At baseline, the median age was 59 (range, 21-81) years, 79% of patients had stage III or IV disease, and 74% of patients had primary refractory disease.

The patients were randomly assigned to receive axi-cel (n=180) or standard care (n=179), which consisted of investigator-selected platinum-based chemoimmunotherapy, followed by HDT-ASCT in responders.

In the axi-cel arm, 170 patients received an axi-cel infusion after lymphodepletion. In the standard care arm, 168 patients received chemoimmunotherapy, and 64 underwent HDT-ASCT. Fifty-seven percent of patients in the standard care arm went on to receive third-line cellular immunotherapy off protocol.

Prior results from this trial showed that axi-cel improved event-free survival (EFS) at a median follow-up of 24.9 months.² The median EFS was 8.3 months in the axi-cel arm and 2.0 months in the standard care arm (hazard ratio [HR], 0.40; 95% CI, 0.31-0.51; P <.001).

In the current analysis, the median follow-up was 47.2 months.¹ The median OS was not reached in the axi-cel arm and was 31 months in the standard care arm (HR, 0.726; 95% CI, 0.540-0.977; P =.0168). The 4-year OS rate was 54.6% in the axi-cel arm and 46.0% in the standard care arm.

“To our knowledge, ZUMA-7 is the first randomized trial in any cancer to show an overall survival benefit for a CAR T-cell therapy over an existing standard of care,” Dr Westin said. “And this is the first trial in nearly 30 years to significantly improve overall survival in the second-line setting for patients with large B-cell lymphoma receiving curative-intent therapy.”

“This conclusively demonstrates that trying chemotherapy in second line and saving cell therapy for third line is an inferior approach,” he added. “With a median follow-up of 47.2 months, these mature survival data are consistent with curative therapy.”

Dr Westin noted that progression-free survival (PFS) was superior with axi-cel as well. The median PFS was 14.7 months in the axi-cel arm and 3.7 months in the standard care arm (HR, 0.506; 95% CI, 0.383-0.669; P <.0001). The 4-year PFS rates were 41.8% and 24.4%, respectively.

Any-grade cytokine release syndrome (CRS) was observed in 92% of patients in the axi-cel arm, and grade 3 or higher CRS was observed in 6%. The rate of neurologic events was 61% in the axi-cel arm and 20% in the standard care arm. The rate of grade 3 or higher neurologic events was 21% and 1%, respectively.

There was 1 confirmed treatment-related death in the axi-cel arm (hepatitis B reactivation) and 2 in the standard care arm (cardiac arrest and acute respiratory distress syndrome).

Disclosures: This research was supported by Kite. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References

1. 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. ASCO 2023. June 2-6, 2023. Abstract LBA107.

2. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large b-cell lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133

This article originally appeared on Hematology Advisor