Axi-Cel Shows Significant OS Improvement in R/R Large B-Cell Lymphoma

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Axicabtagene ciloleucel (axi-cel; Yescarta) has achieved a statistically significant improvement in overall survival (OS) compared with standard-of-care (SOC) therapy for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) who were treated within a year of completing first-line therapy.¹

The results come from the phase 3, randomized, open-label ZUMA-7 study (NCT03391466), which is the largest clinical trial of a chimeric antigen receptor (CAR) T-cell therapy with the longest follow-up and the first to demonstrate event-free survival (EFS) improvement compared with SOC. OS findings from the study will be presented at an upcoming medical meeting.

The SOC initial treatment for relapsed/refractory LBCL is high-dose chemotherapy with autologous stem-cell transplantation (ASCT) for patients whose disease is responsive to chemoimmunotherapy.² Historically, there have been patients who do not respond to salvage chemotherapy. For patients who are ineligible to receive high-dose chemotherapy with ASCT, outcomes are dismal.³

Previously in ZUMA-7, the primary end point of EFS was met. Treatment with axi-cel resulted in a 60% EFS improvement compared with SOC. The estimated 18-month EFS rate was 41.5% (95% CI, 34.2-48.6) with axi-cel vs 17.0% (95% CI, 11.8-23.0) with SOC. The estimated median EFS was 8.3 months (95% CI, 4.5-15.8) with axi-cel vs 2.0 months (95% CI, 1.6-2.8) with SOC.²

Regarding a key secondary end point of ZUMA-7, axi-cel performed better than SOC in the study. The objective response rate was 83% with axi-cel vs 50% with SOC (odds ratio, 5.31; 95% CI, 3.1-8.9; P < .0001). Responses included complete response in 65% of patients treated with axi-cel vs 32% of those treated with SOC.

Grade 3 or higher adverse effects (AEs) occurred in 91% of patients treated with axi-cel compared with 83% of those treated with SOC. The most common grade 3 or higher AEs were neutropenia (69% vs 41%, respectively), anemia (30% vs 39%), and leukopenia (29% vs 22%). Grade 3 or higher serious AEs occurred in 42% of the axi-cel arm compared with 40% of the SOC arm.

Data from ZUMA-7 recently led to theFDA approval of axi-cel for the treatment of adult patients with LBCL that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy.

ZUMA-7 is a randomized, open-label, multicenter study of 359 patients with LBCL who had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous hematopoietic stem cell transplantation. Patients were randomized 1:1 to receive axi-cel plus conditioning chemotherapy (n = 180) or SOC with investigator-selected platinum-based chemoimmunotherapy (n = 179). In addition to the primary end point of EFS, the key secondary end points of the study were progression-free survival, safety, and patient-reported outcomes.

Patients were eligible to be treatment in the study if they had LBCL that was relapsed/refractory within 12 months of frontline therapy and had intentions to proceed to HDT-ASCT. Stratification factors included response to frontline therapy and second-line age-adjusted International Prognostic Index score. Patients were required to be aged 18 years or older.

_REFERENCES:

_{1. Kite’s Yescarta® CAR T-cell therapy demonstrates a statistically significant improvement in overall survival for initial treatment of relapsed/refractory large b-cell lymphoma. News release. Kite. March 22, 2023. Accessed March 22, 2023. https://bit.ly/3yYHdMu}

_{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}

_{3. Locke F, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019;20(1):31-42. doi:10.1016/S1470-2045(18)30864-7}