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Pivotal ZUMA-1 study: axicabtagene ciloleucel (axi-cel) improves outcome for patients with refractory aggressive non-Hodgkin lymphoma

Outcomes for patients with refractory aggressive non-Hodgkin lymphoma (NHL) are poor with current therapies. Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor (CAR) T cell therapy. The efficacy and safety of this therapy is evaluated in the ZUMA-1 study, the first multicenter trial of axi-cel in refractory, aggressive NHL. Previously, results from the interim analysis (n=62) of ZUMA-1 showed an objective response rate (ORR) of 79%, including a complete response rate of 52%.1 At the EHA 2017 results from the primary analysis of ZUMA-1 were presented.

In this phase 2 trial, 101 patients with diffuse large B cell lymphoma (DLBCL), primary mediastinal B cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) with refractory or relapsed disease, received axi-cel at a target dose of 2 x 106 cells/kg. The primary endpoint for this analysis was ORR in the combined DLBCL, PMBCL, and TFL population. Key secondary endpoints were duration of response (DOR), overall survival (OS), and frequency of adverse events.

111 patients were enrolled and 91% of the patients received axi-cel. With an ORR of 82% (n = 92; p < 0.0001) the study met the primary endpoint.2 The ORR in the modified intent-to-treat population (n = 101) was 82%, including a complete response rate of 54%. These responses were consistent across key covariates including disease subtype, refractory status, stage, and International Prognostic Index score. At a median follow up of 8.7 months, 44% of patients were in response and 39% had a complete response. The median DOR was 8.2 months overall and not reached for patients who achieved a complete response. Median OS was not reached; 80% of patients were still alive at 6 months.

The most common grade ≥3 treatment-emergent adverse events were neutropenia (66%), leukopenia (44%), anemia (43%), febrile neutropenia (31%), and encephalopathy (21%). Grade ≥3 cytokine release syndrome and neurologic events occurred in 13% and 28% of the patients, respectively. As previously reported, there were 3 grade 5 adverse events (3%).

The results demonstrate that axi-cel significantly improved ORR in patients with refractory aggressive NHL. The complete response rate was 7-fold higher compared to historical controls and nearly half the patients had an ongoing response.3 Thus, axi-cel demonstrated significant clinical benefit with a manageable safety profile in patients lacking curative treatment options.


1. Neelapu SS, Locke FL, Bartlett NL, et al. Kte-C19 (anti-CD19 CAR T cells) induces complete remissions in patients with refractory diffuse large B-cell lymphoma (DLBCL): results from the pivotal phase 2 Zuma-1. Blood 2016;128 (22): LBA-6

2. Locke FL, Neelapu SS , Bartlett NL, et al. Clinical and biologic covariates of outcomes in ZUMA-1: a pivotal trial of axicabtagene ciloleucel (Axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (NHL). EHA 2017, oral presentation, abstract S466

3. Crump M, Neelapu SS, et al. Outcomes in refractory aggressive diffuse large B-cell lymphoma (DLBCL): Results from the international SCHOLAR-1 study. J Clin Oncol 2016;34 (suppl May 2016):7516


Speaker Yi Lin


Yi Lin, MD, PhD, Mayo Clinic, Rochester, Minnesota, USA


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