CAR-T shows ‘significant survival benefit’ vs. standard of care in lymphoma subset
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Axicabtagene ciloleucel induced higher response rates than standard therapies among a subset of patients with lymphoma, according to study results presented at the virtual American Society of Gene and Cell Therapy Annual Meeting.
Axicabtagene ciloleucel (Yescarta; Kite Pharma, Gilead), a chimeric antigen receptor T-cell therapy also known as axi-cel, also reduced the risk for death in the standardized comparison analysis of 2-year outcomes among patients treated for relapsed or refractory large B-cell lymphoma.
The study compared SCHOLAR-1 — the largest retrospective analysis of outcomes among patients with advanced large B-cell lymphoma (n = 636) in the pre-CAR T-cell therapy era — with ZUMA-1, the pivotal study of anti-CD19 CAR T-cell therapy among patients with relapsed or refractory large B-cell lymphoma (n = 101).
“There was a significant survival benefit in ZUMA-1 compared with SCHOLAR-1,” Sattva S. Neelapu, MD, professor and deputy chair of the department of lymphoma/myeloma in the division of cancer medicine at The University of Texas MD Anderson Cancer Center, said during a presentation.
The investigators used stratified Cochran-Mantel-Haenszel and Cox proportional hazards models to compare ORs for treatment response and HRs for survival between patients in the two studies. Analyses were standardized to equally weight the proportions of patients according to treatment refractoriness (primary refractory, refractory to two or more lines of therapy, or disease relapse after hematopoietic stem cell transplantation).
A comparison of baseline patient characteristics showed patients in ZUMA-1 tended to be older (aged 65 years, 24% vs. 14%-15%) and more heavily pretreated. Sixty-nine percent of patients in ZUMA-1 received more than three previous lines of therapy compared with 23% in SCHOLAR-1. Patients in ZUMA-1 also appeared more likely to be refractory to second-line or later therapy than those in SCHOLAR-1 (76% vs 62%).
The standardized objective response rate in ZUMA-1 was 72% compared with 22% in SCHOLAR-1 (OR = 7.2; 95% CI, 4.37-12.05). Complete response rates after standardization were 54% in ZUMA-1 vs. 7% in SCHOLAR-1 (OR = 11.46; 95% CI, 6.79-19.28).
The 2-year standardized OS rate was 50% in ZUMA-1 compared with 12% in SCHOLAR-1. This equates to a 73% reduction in the risk for death for patients who received axicabtagene ciloleucel vs. standard-of-care treatments (HR = 0.27; P < .0001).
“Standardized analyses of ZUMA-1 vs. SCHOLAR-1 indicate a survival benefit in response rates and overall survival with axi-cel compared with salvage regimens in refractory large B-cell lymphoma,” Neelapu said. “Although limited by retrospective analysis and cross-study comparisons, these findings support those of previous studies indicating that axi-cel is a highly effective treatment option for patients with refractory large B-cell lymphoma.”
Perspective
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Henry Chi Hang Fung, MD, FACP, FRCPE
Outcomes of patients with relapsed or refractory diffuse large B-cell lymphoma typically are dismal. This retrospective study by Neelapu and colleagues clearly demonstrated that axicabtagene ciloleucel compared favorably with conventional salvage therapy.
Achieving a complete response to therapy is the strongest predictive factor for long-term survival and possible cure. Unfortunately, objective response rates for patients treated with axicabtagene ciloleucel remain disappointing at 22%. There certainly is a lot of room for improvement.
In addition, only 26% of patients in the axicabtagene ciloleucel group had primary refractory disease, which is not adequate to evaluate the impact of axicabtagene ciloleucel on this subgroup of patients with a worse prognosis.
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Neelapu SS, et al. Abstract 1344. Presented at: ASGCT Annual Meeting; May 11-15, 2020 (virtual meeting).
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