Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial
- Author(s)
- Neelapu, SS; Dickinson, M; Munoz, J; Ulrickson, ML; Thieblemont, C; Oluwole, OO; Herrera, AF; Ujjani, CS; Lin, Y; Riedell, PA; Kekre, N; de Vos, S; Lui, C; Milletti, F; Dong, J; Xu, H; Chavez, JC;
- Details
- Publication Year 2022-04,Volume 28,Issue #4,Page 735-742
- Journal Title
- Nature Medicine
- Publication Type
- Research article
- 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.
- Keywords
- Antigens, CD19; *Biological Products/adverse effects; Cytokine Release Syndrome; Humans; Immunotherapy, Adoptive/adverse effects; *Lymphoma, Large B-Cell, Diffuse/therapy; Neoplasm Recurrence, Local
- Department(s)
- Haematology
- PubMed ID
- 35314842
- Publisher's Version
- https://doi.org/10.1038/s41591-022-01731-4
- Open Access at Publisher's Site
https://doi.org/10.1038/s41591-022-01731-4- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-02-07 07:07:08
Last Modified: 2025-02-07 07:08:20