Axicabtagene ciloleucel shows promise as frontline therapy for high-risk large B-cell lymphoma

April 2022 Pharma News Nalinee Pathak
Diffuse Large B-Cell Lymphoma (DLBCL) of Stomach is a rare, B-cell non-Hodgkin’s lymphoma that affects older adults. It is a subtype of lymphoma of stomach that is more aggressive and rapid-growing than other subtypes. In majority of cases, the lymphoma is a type of primary non-Hodgkin lymphoma. This means that it first involves the stomach and later can involve other parts of the body including the lymph nodes and bone marrow.

The results of the ZUMA-12 trial indicate considerable activity of axicabtagene ciloleucel (axi-cel) as first-line therapy for large B cell lymphoma (LBCL). These findings were published recently in the journal Nature Medicine.

Despite currently available standard first-line chemoimmunotherapy treatment, the clinical outcomes of LBCL patients remain poor. Researchers from the University of Texas MD Anderson Cancer Center have evaluated the efficacy of axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell, as a new first-line treatment option for LBCL patients.

Study design

The phase-2, single-arm, multicenter, ZUMA-12 study enrolled 40 patients with high-risk LBCL to evaluate the efficacy of CAR-T cell therapy, axi-cel as part of first-line treatment. The majority (95%) of patients have stage III/IV disease, 25% had double or triple hit status, and 78% had an IPI score ≥3. The study’s primary outcome was complete response rate (CRR), and secondary outcomes included objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), and overall survival (OS).  

Main findings

In the efficacy-evaluable (n=37) patients, 78%  experienced complete response (95% confidence interval (CI), 62–90) and 89% had ORR ((95% CI, 75–97). After a median follow up of 15.9 months (data cut-off), 73% of patients had an ongoing response. However, the median for DOR, EFS and PFS were not reached. No treatment-related events (TREs) of grade 5 were observed. However, grade 3 TREs such as cytokine release syndrome (CRS) and neurologic events occurred in three (8%) and nine patients (23%), respectively.


The findings of the ZUMA-12 trial demonstrate the effectiveness of CAR-T cell first-line therapy for LBCL patients.


Neelapu, S.S., Dickinson, M., Munoz, J. et al. Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Nat Med (2022).