Axicabtagene ciloleucel (axi-cel) improves outcomes when compared with standard second-line treatment in patients with relapsed/refractory large B-cell lymphoma (LBCL), according to the primary analysis of the ZUMA-7 trial.
Axi-cel doubled the complete response (CR) rate and quadrupled the median event-free survival (EFS) when compared with the standard of care (SOC).
“Results of ZUMA-7 herald a paradigm shift. Axicabtagene ciloleucel should be a new standard for patients with second-line relapsed/refractory large B-cell lymphoma,” said Frederick L. Locke, MD, of Moffitt Cancer Center in Tampa, Florida.
Dr Locke presented these results at the 2021 American Society of Hematology (ASH) Annual Meeting.1 The study was also published in the New England Journal of Medicine.2
In the phase 3 trial (ClinicalTrials.gov Identifier: NCT03391466), Dr Locke and colleagues compared second-line SOC with a single dose of axi-cel, an autologous anti‑CD19 chimeric antigen receptor (CAR) T-cell therapy.
Patients in the SOC arm first received 1 of 4 investigator-selected platinum-based chemoimmunotherapy regimens. Patients who responded to this treatment went on to receive high-dose therapy and autologous stem cell transplant (HDT-ASCT).
The study enrolled 359 patients with relapsed/refractory LBCL. The median age was 59 years (range, 21-81 years), 79% of patients had stage III/IV disease, and 74% had primary refractory disease.
Of the 180 patients randomly assigned to receive axi-cel, 170 (94%) were ultimately infused. Of the 179 patients randomly assigned to SOC, 64 (36%) ultimately received HDT-ASCT. The median follow-up was 24.9 months.
The median EFS was 8.3 months with axi-cel and 2.0 months with SOC (hazard ratio [HR], 0.398; 95% CI, 0.308-0.514; P <.0001). The estimated 2-year EFS rate was 40.5% and 16.3%, respectively.
The overall response rate was 83% with axi-cel and 50% with SOC (odds ratio, 5.31; 95% CI, 3.1-8.9; P <.0001). The CR rate was 65% and 32%, respectively.
The median overall survival (OS) was not reached in the axi-cel arm and was 35.1 months in the SOC arm. This did not reach statistical significance (HR, 0.730; 95% CI, 0.530-1.007; P =.027).
Dr Locke said OS was likely confounded by treatment switching. In the SOC arm, 56% of patients received subsequent treatment with cellular immunotherapy, such as CAR T-cell therapy, off protocol.
Grade 3 or higher treatment-emergent adverse events were observed in 91% of patients in the axi-cel arm and 83% in the SOC arm. Treatment-related death was reported in 1 patient in the axi-cel arm and 2 patients in the SOC arm.
In the axi-cel arm, grade 3 or higher cytokine release syndrome (CRS) occurred in 6% of patients. The median time to CRS onset was 3 days, and the median duration was 7 days.
Grade 3 or higher neurologic events occurred in 21% of patients in the axi-cel arm. The median time to onset was 7 days, and the median duration was 9 days.
There were no cases of grade 5 CRS or neurologic events reported during the study.
Disclosures: ZUMA-7 was sponsored by Kite, a Gilead company. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Read more of Cancer Therapy Advisor’s coverage of the ASH 2021 meeting by visiting the conference page.
1. Locke FL, Miklos DB, Jacobson C, et al. Primary analysis of ZUMA‑7: A phase 3 randomized trial of axicabtagene ciloleucel (axi-cel) versus standard‑of‑care therapy in patients with relapsed/refractory large B-cell lymphoma. Presented at ASH 2021; December 11-14, 2021. Abstract 2.
2. Locke FL, Miklos DB, Jacobson C, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. Published online December 11, 2021. doi:10.1056/NEJMoa2116133