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

Abstract

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 (ClinicalTrials.gov 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.

• Authors: 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
• Journal: Nature medicine (Nat Med) Vol. 28 Issue 4 Pg. 735-742 (04 2022) ISSN: 1546-170X [Electronic] United States
• PMID: 35314842 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: © 2022. The Author(s).

Chemical References

• Antigens, CD19
• Biological Products
• axicabtagene ciloleucel

Topics

• Antigens, CD19
• Biological Products (adverse effects)
• Cytokine Release Syndrome
• Humans
• Immunotherapy, Adoptive (adverse effects)
• Lymphoma, Large B-Cell, Diffuse (therapy)
• Neoplasm Recurrence, Local