Journal Article

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

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

2022

Overview

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. In a phase 2 trial, first-line treatment with axicabtagene ciloleucel, an autologous CD19-targeting CAR T-cell therapy, exhibited a high complete response rate and a manageable safety profile in adults with high-risk large B-cell lymphoma.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/308/2779/109/1941 / 692/699/67/1059/2325 / 692/699/67/1990/291/1621/1915 / Antigens / Antigens, CD19 / B-cell lymphoma / Biological Products - adverse effects / Biomedical and Life Sciences / Biomedicine / Blood levels / Cancer Research / CD19 antigen / Cell therapy / Central nervous system / Chemotherapy / Chimeric antigen receptors / Confidence intervals / Cytokine Release Syndrome / Cytokines / Humans / Immunotherapy / Immunotherapy, Adoptive - adverse effects / Infectious Diseases / Lymphocytes / Lymphocytes B / Lymphocytes T / Lymphoma / Lymphoma, Large B-Cell, Diffuse - therapy / Metabolic Diseases / Molecular Medicine / Neoplasm Recurrence, Local / Neurosciences / Patients / Response rates / Risk / Safety / Safety management / Survival / Therapy