Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial

Sattva S. Neelapu, Michael Dickinson, Javier Munoz, Matthew L. Ulrickson, Catherine Thieblemont, Olalekan O. Oluwole, Alex F. Herrera, Chaitra S. Ujjani, Yi Lin, Peter A. Riedell, Natasha Kekre, Sven de Vos, Christine Lui, Francesca Milletti, Jinghui Dong, Hairong Xu, Julio C. Chavez

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High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study ( NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40 patients with high-risk LBCL. This trial has completed accrual. The primary outcome was complete response rate (CRR). Secondary outcomes were objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse and blood levels of CAR T cells and cytokines. The primary endpoint in efficacy-evaluable patients (n = 37) was met, with 78% CRR (95% confidence interval (CI), 62–90) and 89% ORR (95% CI, 75–97). As of 17 May 2021 (median follow-up, 15.9 months), 73% of patients remained in objective response; median DOR, EFS and PFS were not reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. There were no treatment-related grade 5 events. Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8 days. We conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile.

Original languageEnglish (US)
Pages (from-to)735-742
Number of pages8
JournalNature Medicine
Issue number4
StatePublished - Apr 2022

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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