Three-year follow-up analysis of first-line axicabtagene ciloleucel for high-risk large B-cell lymphoma: the ZUMA-12 study

ZUMA-12 is a multicenter phase 2 study evaluating axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy as part of first-line treatment for high-risk large B-cell lymphoma (LBCL). In the primary efficacy analysis (n = 37; median follow-up, 15.9 months), axi-cel demonstrated a high rate of complete responses (CR; 78%) and a safety profile consistent with prior experience. Here, we assessed updated outcomes from ZUMA-12 in 40 treated patients after ≥3 years of follow-up. Eligible adults underwent leukapheresis, lymphodepleting chemotherapy, and axi-cel infusion (2 × 106 CAR T cells/kg). Investigator-assessed CR, objective response, survival, safety, and CAR T-cell expansion were assessed. The CR rate among response-evaluable patients (n = 37) increased after the primary analysis to 86% (95% confidence interval [CI], 71%-95%), with a 92% objective response rate. After a median follow-up of 47.0 months (range, 37.1-57.8 months), 36-month estimates (95% CI) of duration of response and event-free, progression-free, and overall survival were 81.8% (63.9%-91.4%), 73.0% (55.6%-84.4%), 75.1% (57.5%-86.2%), and 81.1% (64.4%-90.5%), respectively. In total, 4 patients had new malignancies, 2 occurring after the data cutoff of the primary analysis; none were axi-cel-related. Eight patients died on study, 2 of whom died from nonrelapse mortality causes. After long-term follow-up, axi-cel demonstrated a high durable response rate, with no new safety signals after the primary analysis, suggestive of an effective first-line therapy with curative intent in high-risk LBCL. Further assessments are needed to determine its benefit vs standard of care. This trial was registered at clinicaltrials.gov, as NCT03761056.

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Journal
Blood
Published
2025-02-12
DOI
https://doi.org/10.1182/blood.2024027347
Citations
17
Primary Topic
CAR-T cell therapy research
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article
Field-Weighted Citation Impact
17.77
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article

Three-year follow-up analysis of first-line axicabtagene ciloleucel for high-risk large B-cell lymphoma: the ZUMA-12 study

Peter A. Riedell, Natasha Kekre, Matthew L. Ulrickson, Ioana Kloos et al.
17 citations
Blood
CAR-T cell therapy research
17.77
article

Three-year follow-up analysis of first-line axicabtagene ciloleucel for high-risk large B-cell lymphoma: the ZUMA-12 study

Peter A. Riedell, Natasha Kekre, Matthew L. Ulrickson, Ioana Kloos, Alex Francisco Herrera, Catherine Thiéblemont, Olalekan O. Oluwole, Jacob Wulff, Chad M. Williams, Sattva Swarup Neelapu, Chaitra S. Ujjani, Sven de Vos, Joshua D. Winters, Julio C. Chávez, Javier Muñoz, Yi Lin, Michael John Dickinson, Hairong Xu
article en
17 citations

Abstract

ZUMA-12 is a multicenter phase 2 study evaluating axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy as part of first-line treatment for high-risk large B-cell lymphoma (LBCL). In the primary efficacy analysis (n = 37; median follow-up, 15.9 months), axi-cel demonstrated a high rate of complete responses (CR; 78%) and a safety profile consistent with prior experience. Here, we assessed updated outcomes from ZUMA-12 in 40 treated patients after ≥3 years of follow-up. Eligible adults underwent leukapheresis, lymphodepleting chemotherapy, and axi-cel infusion (2 × 106 CAR T cells/kg). Investigator-assessed CR, objective response, survival, safety, and CAR T-cell expansion were assessed. The CR rate among response-evaluable patients (n = 37) increased after the primary analysis to 86% (95% confidence interval [CI], 71%-95%), with a 92% objective response rate. After a median follow-up of 47.0 months (range, 37.1-57.8 months), 36-month estimates (95% CI) of duration of response and event-free, progression-free, and overall survival were 81.8% (63.9%-91.4%), 73.0% (55.6%-84.4%), 75.1% (57.5%-86.2%), and 81.1% (64.4%-90.5%), respectively. In total, 4 patients had new malignancies, 2 occurring after the data cutoff of the primary analysis; none were axi-cel-related. Eight patients died on study, 2 of whom died from nonrelapse mortality causes. After long-term follow-up, axi-cel demonstrated a high durable response rate, with no new safety signals after the primary analysis, suggestive of an effective first-line therapy with curative intent in high-risk LBCL. Further assessments are needed to determine its benefit vs standard of care. This trial was registered at clinicaltrials.gov, as NCT03761056.

BloodVol. 145(20)
City Of Hope National Medical Center (US), The Royal Melbourne Hospital (AU), Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), Mayo Clinic (US), Seattle Cancer Care Alliance (US), The University of Texas MD Anderson Cancer Center (US), Vanderbilt University (US), Peter MacCallum Cancer Centre (AU), Ottawa Hospital (CA), University of California System (US), Moffitt Cancer Center (US), University of Chicago (US), Fred Hutch Cancer Center (US), Assistance Publique – Hôpitaux de Paris (FR), City of Hope (US), Mayo Clinic in Arizona (US), Kite (United States) (US), Hôpital Saint-Louis (FR), Mayo Clinic in Florida (US), Banner MD Anderson Cancer Center, Vanderbilt University Medical Center (US)
Good health and well-being
Openalex Percentile: Top 1%
CAR-T cell therapy research
17.77
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