The Food and Drug Administration (FDA) has approved Yescarta® (axicabtagene ciloleucel) for the treatment of adults with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.

The approval was based on data from the randomized, open-label, multicenter phase 3 ZUMA-7 trial ( Identifier: NCT03391466), which evaluated the efficacy and safety of axicabtagene ciloleucel, a CD19-directed genetically modified autologous T cell immunotherapy, in adults with relapsed or refractory LBCL after first-line chemoimmunotherapy that included rituximab and anthracycline. 

Patients were randomly assigned 1:1 to receive a single infusion of axicabtagene ciloleucel following fludarabine or cyclophosphamide lymphodepleting chemotherapy (n=180) or standard of care second-line therapy consisting of 2 or 3 cycles of chemoimmunotherapy followed by high-dose therapy and autologous hematopoietic stem cell transplantation in patients who attained complete or partial remission (n=179). The primary endpoint was event-free survival (EFS) determined by an independent review committee.

Results showed that treatment with axicabtagene ciloleucel was associated with a statistically significant improvement in EFS compared with standard therapy (hazard ratio [HR], 0.40; 95% CI, 0.31-0.51; P <.0001). The estimated EFS rate at 18 months was 41.5% (95% CI, 34.2-48.6) in the axicabtagene ciloleucel arm and 17% (95% CI, 11.8-23.0) in the standard therapy arm. The estimated median EFS was 8.3 months (95% CI, 4.5-15.8) in the axicabtagene ciloleucel arm and 2 months (95% CI, 1.6-2.8) in the standard therapy arm.

Additionally, the best objective response rate (secondary endpoint) was found to be statistically significantly higher in the axicabtagene ciloleucel group vs the standard therapy group (83% [95% CI, 77-88]) vs 50% [95% CI, 43-58]; odds ratio, 5.31; 95% CI, 3.1-8.9; P <.0001). The complete remission rate was reported to be 65% (95% CI, 58-72) and 32% (95% CI, 26-40) in the axicabtagene ciloleucel and standard therapy arms, respectively.

“The ZUMA-7 trial enabled us to look at the broader picture of what happens to patients after a decision is made to follow a particular treatment path,” said Frederick L. Locke, MD, ZUMA-7 Principal Investigator and Co-Leader of the Immuno-Oncology Program at Moffitt Cancer Center, Tampa, Florida. “What we found was that axi-cel resulted in 3 times as many patients receiving treatment with curative intent (CAR T-cell therapy), and an overall better outcome for patients than the previous standard of care. Additionally, we have now amassed significant experience with CAR T-cell therapy to better manage or prevent side effects, making this treatment more accessible for older patients and those with medical conditions for whom the standard of care might be difficult.”

Among the 168 axicabtagene ciloleucel-treated patients evaluable for safety, grade 3 or greater cytokine release syndrome and neurologic events were observed in 7% and 25% of patients, respectively. Sixty-seven percent (112/168) of patients received tocilizumab after infusion of axicabtagene ciloleucel. In December 2021, the FDA issued temporary guidance with respect to certain risk evaluation and mitigation strategy (REMS) requirements for CAR T-cell immunotherapies due to an ongoing shortage of tocilizumab related to the COVID-19 pandemic.

“Definitive clinical trial results such as these do not come along often and should drive a paradigm shift in how patients with relapsed or refractory LBCL are treated moving forward,” said Jason Westin, MD, MS, FACP, ZUMA-7 Principal Investigator, Director, Lymphoma Clinical Research, and Associate Professor, Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. “Patients who do not respond to or relapse after initial treatment should quickly be referred to a CAR T-cell therapy authorized treatment center for evaluation.”

Yescarta is already indicated for relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. It is also approved for relapsed or refractory follicular lymphoma after 2 or more lines of systemic therapy.


  1. FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. News release. US Food and Drug Administration. April 1, 2022. Accessed April 4, 2022.
  2. Yescarta® receives US FDA approval as first CAR T-cell therapy for initial treatment of relapsed or refractory large B-cell lymphoma (LBCL). News release. Kite Pharma, Inc. April 1, 2022. Accessed April 4, 2022.
  3. Yescarta. Package insert. Kite Pharma, Inc.; 2022. Accessed April 4, 2022.