In the treatment of relapsed/refractory follicular lymphoma, a comparison of data from the ZUMA-5 trial with those of the external control cohort of the SCHOLAR-5 trial showed substantial improvement in all clinical endpoints with axicabtagene ciloleucel. John G. Gribben, DSc, FRCP, FRCPath, FMedSci, and colleagues reported these findings in a late-breaking abstract at the European Hematology Association 2021 Virtual Congress (LBA1904).
The updated analysis used propensity score methodology to compare clinical outcomes from ZUMA-5 to those from the international SCHOLAR-5 trial. SCHOLAR-5’s external control cohort was generated to provide comparative evidence in patients meeting the ZUMA-5 eligibility criteria. In SCHOLAR-5, patients received multiple lines of “heterogeneous” therapies, said Dr. Gribben, Professor of Medical Oncology at Cancer Research UK Barts Centre, London.
Axicabtagene ciloleucel was superior in terms of objective response rate, time to next treatment, progression-free survival, and overall survival—not only in the overall population but in patients who had received at least three prior lines of treatment.
Median progression-free survival was not reached in the ZUMA-5 cohort but was 12.68 months in the SCHOLAR-5 group (P < .001). Similarly, median overall survival was not reached in ZUMA-5 and was 59.8 months in SCHOLAR-5 patients (P = .0125).
The substantial overall survival benefit suggests that axicabtagene ciloleucel addresses an important unmet medical need for relapsed/refractory follicular lymphoma patients.— John G. Gribben, DSc, FRCP, FRCPath, FMedSci
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The statistically significant improvements over other therapies, even after multiple rounds of prior therapies, highlights “the deep and durable treatment” effect of axicabtagene ciloleucel, said Dr. Gribben, “and the substantial overall survival benefit (hazard ratio [HR] = 0.42, P = .01) suggests that axicabtagene ciloleucel addresses an important unmet medical need for relapsed/refractory follicular lymphoma patients.”
Axicabtagene ciloleucel is the first and only chimeric antigen receptor T-cell therapy approved in patients with relapsed or refractory indolent follicular lymphoma.
About the Studies
ZUMA-5 is an ongoing, single-arm, open-label, multicenter trial evaluating 146 patients with relapsed or refractory indolent non-Hodgkin lymphoma, including follicular lymphoma, who received at least two prior lines of systemic therapy, including the combination of an anti-CD20 monoclonal antibody and an alkylating agent.
SCHOLAR-5 is an international, retrospective external control cohort of patients with relapsed or refractory follicular lymphoma. Data were sourced from seven institutions across five countries of patients treated with a third-line or later regimen, including patients from the DELTA trial of idelalisib, creating a cohort whose treatments are highly heterogeneous.
The researchers analyzed 86 patients from the ZUMA-5 population and 85 patients from SCHOLAR-5, who were propensity-matched to reduce bias in the comparison. Patients had grade 1 or 2 relapsed/refractory follicular lymphoma and had not responded to or progressed after two or more prior lines of treatment. All had an ECOG performance status of 0 or 1. ZUMA-5 eligibility criteria were applied to the SCHOLAR-5 cohort, with patients excluded or censored upon transformation.
After propensity score weighting, baseline characteristics were similar between the groups in terms of median age (approximately 63 years), prior treatment (median = approximately 3.5), percentage refractory to last line of treatment (approximately 75%), percentage with stem cell transplant (approximately 26%), time since last treatment (approximately 8 months) and median time since diagnosis (76 months).
All Outcomes Significantly Better With Axicabtagene Ciloleucel
The ZUMA-5 cohort, treated with axicabtagene ciloleucel, had significantly better outcomes in all major endpoints as compared to the SCHOLAR-5 cohort, who were treated with a variety of other options:
- Objective response rates: 94.2% vs 49.9% (odds ratio [OR] = 16.24, P < .0001)
- Complete response rates: 79.1% vs 29.9% (OR = 8.86, P < .0001)
- Median progression-free survival: not reached vs 12.69 months (HR = 0.30, P < .001)
- Median overall survival: not reached vs 59.8 months (HR = 0.42, P = .0125)
- Median time to next treatment: not reached vs 14.43 months (HR = 0.42, P < .001).
All these improvements with axicabtagene ciloleucel were seen in the overall population and for the cohort of patients treated with three or more prior therapies. In fact, for overall survival, in the more refractory patients, axicabtagene ciloleucel exerted even greater benefit (HR = 0.31) than for the overall cohort (HR = 0.42).
“These data certainly support that axicabtagene ciloleucel represents a significant improvement in treatment options for patients with relapsed/refractory follicular lymphoma,” Dr. Gribben commented.
In the ZUMA-5 safety analysis set (n = 146), grade ≥ 3 cytokine-release syndrome and neurologic toxicities occurred in 8% and 21% of patients, respectively.
Commentary
Caron A. Jacobson, MD, MMSc
“In an indolent disease like follicular lymphoma, longer-term data that demonstrate durable responses are critical. After a patient with follicular lymphoma relapses, the duration of response shortens with each new therapy,” added ZUMA-5 co-investigator Caron A. Jacobson, MD, MMSc, Medical Director, Immune Effector Cell Therapy Program, Dana-Farber Cancer Institute and Assistant Professor of Medicine, Harvard Medical School.
“The continued durable benefit demonstrated by axicabtagene ciloleucel at nearly 2 years is exciting, and the substantial survival benefit over current therapies that we’re seeing in the SCHOLAR-5 analysis is encouraging. These follow-up data reinforce axicabtagene ciloleucel as an important advance for a group of patients who have historically had few options.”
Disclosure: For full disclosures of the study authors, visit library.ehaweb.org.
