Updated 5-year data from the phase 2 ZUMA-5 trial demonstrate that axicabtagene ciloleucel (axi-cel; Yescarta) provides durable responses and long-term survival benefits for patients with relapsed/refractory follicular lymphoma (FL) and marginal zone lymphoma (MZL). The findings, presented at the 2024 ASH Annual Meeting, underscore the potential of axi-cel as a highly effective therapeutic option for these patients.
Long-Term Efficacy Data
The ZUMA-5 trial (NCT03105336) enrolled 159 patients with relapsed or refractory FL (n = 127) and MZL (n = 31) who had previously received at least two lines of systemic therapy, including an anti-CD20 monoclonal antibody and an alkylating agent. With a median overall follow-up of 64.6 months, the data reveal compelling efficacy outcomes.
The overall response rate (ORR) across all treated patients was 90%, comprising a complete response (CR) rate of 75% and a partial response (PR) rate of 14%. Specifically, in the FL group, the ORR was 94% with a CR rate of 79%, while the MZL group showed an ORR of 77% and a CR rate of 65%.
The median duration of response (DOR) was 60.4 months (95% CI, 39.7-NE) overall, with a median DOR of 60.4 months (95% CI, 36.6-NE) in the FL group and not reached (95% CI, 13.9-NE) in the MZL cohort. The ongoing response rate overall was 44%, including 43% and 48% in the FL and MZL cohorts, respectively. Among patients who achieved a CR, 58% remained in CR at the March 31, 2024, data cutoff.
The landmark 60-month progression-free survival (PFS) rate was 50.4% (95% CI, 41.3%-58.7%) across all patients, including 49.8% (95% CI, 39.8%-59.0%) and 53.9% (95% CI, 32.9%-71.0%) in the FL and MZL groups, respectively. The 5-year median PFS was 62.2 months (95% CI, 34.9-NE), comprising a median PFS of 57.3 months in the FL arm and NR in the MZL group. Among patients who had a CR, the 5-year PFS rate was 61.9% and among patients with a PR, the 5-year PFS rate was 9.1%. Notably, in patients with FL the 5-year PFS benefit was observed across high-risk subgroups, such as those who progressed less than 2 years from starting their first anti-CD20–containing chemoimmunotherapy.
The median overall survival (OS) was not reached at 5 years, and the estimated 60-month OS rate was 69% overall, and 68.9% and 71.1% in the FL and MZL cohorts, respectively. The median time to next therapy was not reached in either of the cohorts. Eighty-seven patients (55%) were alive with no new anticancer treatment at the data cutoff.
Safety Profile
Safety data were reported for all 152 treated patients (FL, n = 124; MZL, n = 28). Since the previous 4-year analysis, no new safety signals emerged, and no patients died due to disease progression. Three new events occurred that were unrelated to axi-cel treatment: a grade 3 metastasis, grade 1 bladder cancer, and grade 4 myelodysplastic syndrome. Further, there was 1 patient death due to pneumonia that was not related to axi-cel treatment. A total of 46 patients died at any time on the trial: progressive disease (PD) or a non-PD event after PD (n = 23), secondary malignancies (n = 6), cardiac event (n = 3), infection-related (n = 11), other (n = 3).
Clinical Implications
“Collectively, these long-term data support axi-cel as a highly effective therapeutic approach for patients with R/R indolent non-Hodgkin lymphoma, with curative potential in patients with FL,” said Sattva S. Neelapu, MD, The University of Texas MD Anderson Cancer Center, Houston, TX.
The FDA approved axi-cel in March 2021 for the treatment of adult patients with relapsed or refractory FL after two or more lines of systemic therapy, based on earlier results from the ZUMA-5 trial. These updated findings reinforce its role as a valuable treatment option, offering sustained remission and improved survival for patients with relapsed/refractory indolent lymphomas.
