Axi-cel exhibits durable benefit in advanced indolent non-Hodgkin lymphoma
Key takeaways:
- Axicabtagene ciloleucel induced durable responses for patients with relapsed or refractory indolent non-Hodgkin lymphoma.
- Median response duration exceeded 5 years.
SAN DIEGO — Treatment with axicabtagene ciloleucel conferred durable benefit to patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma, according to study results presented at ASH Annual Meeting and Exposition.
More than half of treated patients remained alive with no new anti-cancer therapy after 5-plus years of follow-up, long-term data from the phase 2 ZUMA-5 trial showed.
The findings suggest the agent is “highly effective” in this setting, according to researcher Sattva S. Neelapu, MD, professor in the department of lymphoma-myeloma in the division of cancer medicine at The University of Texas MD Anderson Cancer Center.
“Remarkably, the median PFS and overall survival were not reached after 5 years,” Neelapu told Healio. “Importantly, only four patients progressed beyond 2 years, and we observed a plateau in the lymphoma-specific PFS.
“The efficacy was consistent regardless of high-risk factors [among patients with follicular lymphoma],” Neelapu added. “These results are markedly superior to any other available therapies in the third-line setting and beyond for these patients.”
Background and methods
Axicabtagene ciloleucel (Yescarta, Kite Pharma/Gilead Sciences) — often called axi-cel — is a CD19-directed chimeric antigen receptor T-cell therapy.
The FDA approved the agent — based on earlier results of ZUMA-5 — for treatment of patients with relapsed or refractory follicular lymphoma who received two or more lines of systemic therapy, including an anti-CD20 monoclonal antibody plus an alkylating agent.
The trial enrolled 159 patients with relapsed or refractory non-Hodgkin lymphoma (follicular lymphoma, n = 127; marginal zone lymphoma, n = 31).
Patients received a lymphodepleting chemotherapy regimen that included cyclophosphamide and fludarabine, followed by an infusion of axi-cel dosed at 2 x 106 CAR T cells/kg.
ORR served as the primary endpoint.
Previously reported results based on median follow-up of at least 52 months showed median PFS of 57.3 months for trial participants with follicular lymphoma and 46.9 months for those with marginal zone lymphoma.
At ASH, Neelapu and colleagues presented updated data based on median follow-up of 64.6 months (range, 32.3-81.4).
Results, next steps
Updated results showed a 90% ORR and a 75% complete response rate, Neelapu said.
Median duration of response reached 60.4 months (95% CI, 39.7 to not estimable), with more than half (53.4%; 95% CI, 43.9-62) of trial participants remaining in response for at least 60 months.
At data cutoff, 58% of those who achieved complete response remained in complete response.
Researchers reported median PFS of 62.2 months (95% CI, 34.9 to not estimable). About half (50.4%) of all patients remained progression free at 60 months, with a slightly higher percentage of those with marginal zone lymphoma than follicular lymphoma achieving 60-month PFS (53.9% vs. 49.8%).
PFS rates at 60 months for patients with follicular lymphoma remained consistent regardless of variation in high-risk characteristics, such as progression at less than 2 years from initiating first anti-CD20-containing chemoimmunotherapy.
Median PFS had not been reached (95% CI, 62.2 months to not estimable) at data cutoff among the 120 patients who achieved complete response. Results showed median PFS of 6.9 months (95% CI, 4.5-12.4) among the 23 patients who achieved partial response.
Median time to next therapy had not been reached in the overall study population (95% CI, 38.6 months to not estimable).
At data cutoff, 87 patients (55%) remained alive with no new anticancer therapy.
Median OS had not been reached in the overall study population. Researchers reported an estimated 60-month OS rate of 69% (95% CI, 60.8-75.8), with a comparable percentage of those with follicular lymphoma (68.9%) and marginal zone lymphoma (71.1%) remaining alive at 5 years.
Four patients progressed more than 24 months after leukapheresis, and one patient progressed after data cutoff of the 4-year analysis. No patients died of disease progression after the prior analysis.
Among the 152 patients who received treatment (follicular lymphoma, n = 124; marginal zone lymphoma, n = 28), three new events not related to axi-cel occurred after the 4-year analysis. These included grade 3 metastasis, grade 1 bladder cancer and grade 4 myelodysplastic syndrome.
One patient died of pneumonia unrelated to axi-cel treatment; 47 patients died during the trial due to progressive disease (n = 14), secondary malignancies (n = 6), infections (n = 15) or other/unknown causes (n = 12).
The randomized phase 3 ZUMA-22 trial is ongoing to compare axi-cel with standard therapy for patients with relapsed or refractory follicular lymphoma, Neelapu said.
“It is likely that moving the therapy to earlier lines may further improve efficacy, as the T cells are expected to be fitter,” Neelapu told Healio. “Accordingly, the ZUMA-22 study will include patients after two prior lines, as well as high-risk patients after one prior line of therapy. Mechanisms associated with relapse and resistance also need to be explored to develop novel combination strategies to further improve outcomes [for] these patients.”
Perspective
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Perspective
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Additional investigation regarding the role of axi-cel in follicular lymphoma management is now underway with ZUMA-22, a randomized controlled phase 3 of axi-cel vs. standard-of-care therapy. This follow-up study is enrolling patients with follicular lymphoma who have had either had one prior line of therapy and progressed in less than 2 years, or those who had two or more prior lines of systemic therapy. Combined, the results of this subsequent study and the maturing data from ZUMA-5 likely will provide significant clarity regarding the expanding role of axi-cel in indolent non-Hodgkin lymphoma management.
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Neelapu SS, et al. Abstract 864. Presented at: ASH Annual Meeting and Exhibition; Dec. 7-10, 2024; San Diego.