Treatment with axicabtagene ciloleucel (axi-cel) resulted in a higher response rate and similar survival and toxicity outcomes as the original trial among patients with refractory diffuse large B-cell lymphoma (DLBCL), many of whom would not have been eligible for the original trial, according to results of a retrospective study published in the Journal of Clinical Oncology.1

Axi-cel was approved by the US Food and Drug Administration based on the 82% overall and 54% complete response rates in the ZUMA-1 trial. But the ZUMA-1 trial, and the JULIET trial for another chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, included highly selected patients.

“The assumption is that included patients and diseases do not reflect the real world,” the authors wrote. The purpose of this retrospective study was to determine the outcomes with axi-cel in a commercial setting, which included patients outside the eligibility criteria of the ZUMA-1 trial.

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The multicenter study included 122 adults with refractory DLBCL, 62% of whom would have been ineligible for ZUMA-1 due to the use of bridging therapy and/or their disease characteristics. All patients received axi-cel with a median follow-up of 10.4 months.

The median patient age of the cohort was 62 years, and 91% had an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients who would have been ineligible for ZUMA-1 were more likely to have a higher performance status, a higher International Prognostic Indicator score, a higher median C-reactive protein at infusion, and had received bridging therapy.

The overall response rate (ORR) was 70%, with 50% of patients achieving a complete response (CR) and 20% achieving a partial response (PR). The median duration of response (DOR) was 1 months. The median progression-free survival (PFS) was 4.5 months (95% CI, 3.2-12.1 months) and the median overall survival (OS) was not yet reached. At 1 year, the OS was 67% (95% CI, 59%-77%).

Patients who achieved a CR had improved outcomes compared with the larger cohort. In this subset, the median DOR and PFS were not reached.

Among the patients who would have been ineligible for ZUMA-1, the ORR was 68% compared with 70% in the eligible group. The CR rate was lower at 42% in the ineligible group compared with 63% in the eligible group. Similarly, median DOR, PFS, and OS were lower among ZUMA-1 ineligible patients.

These rates are much higher than would be expected among patients with refractory DLBCL. Authors of an editorial published simultaneously in the Journal of Clinical Oncology noted an ORR of 26% and a CR of 7% with chemotherapy in the retrospective SCHOLAR-1 study.2

In this cohort, 93% of patients developed cytokine release syndrome (CRS), with 16% being of grade 3 or higher, and 1 death.1 Neurotoxicity occurred in 70% of patients, and was grade 3 or higher in 35% of cases. There was 1 death due to neurotoxicity. The nonrelapsing mortality rate was 6%.

All deaths occurred in patients who were ZUMA-1 ineligible, although the rates of CRS and neurotoxicity were similar with ZUMA-1–eligible patients.

“Axi-cel in the nontrial setting retains its efficacy, with a similar safety profile,” the authors of the study concluded. They noted that although there were differences in outcomes between ZUMA-1 eligible and ineligible patients, “CAR T cells do yield durable responses in this latter group as well.”

In the accompanying editorial, the authors pointed out that the centers involved in this study were experienced in CAR-T therapies and were involved in CAR-T trials.2 “Investigators and their teams were likely well trained to select and manage patients who were candidates and were treated with axi-cel.” Therefore, “it would be important to further confirm the results.”


  1. Jacobson CA, Hunter BD, Redd R, et al. Axicabtagene ciloleucel in the non-trial setting: outcomes and correlates of response, resistance, and toxicity [published online July 15, 2020]. J Clin Oncol. doi: 10.1200/JCO.19.02103
  2. Ghesquieres H, Salles G. Early off-study experience of chimeric antigen receptor T cells in aggressive lymphoma: closer to a real-world setting [published online July 15, 2020]. J Clin Oncol. doi: 10.1200/JCO.20.01134