FDA Approves Axi-Cel for Relapsed/Refractory Indolent Follicular Lymphoma

Mar 6, 2021

The FDA has granted an accelerated approval to axicabtagene ciloleucel for the treatment of adult patients with relapsed/refractory indolent follicular lymphoma after 2 or more lines of systemic therapy.


The FDA has approved axicabtagene ciloleucel (Yescarta) for the treatment of adult patients with relapsed or refractory follicular lymphoma following 2 or more lines of systemic therapy.1

The regulatory decision was based on data from the phase 2 ZUMA-5 trial (NCT03105336), in which the CAR T-cell product elicited a response in 91% of patients with relapsed/refractory follicular lymphoma (n = 81); this included 60% of patients who achieved a complete remission (CR). Notably, 74% of patients had a continued remission at 18 months. Among all patients with follicular lymphoma, the median duration of response (DOR) was not yet reached at a median follow-up of 14.5 months.

“Once a follicular lymphoma patient’s disease relapses, the duration of response to care shortens with each round of therapy,” Caron A. Jacobson, MD, MMSc, medical director of the Immune Effector Cell Therapy Program at Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School, stated in a press release. “Additionally, for patients with follicular lymphoma in the third line of therapy, the 5-year survival rate is only 20%, highlighting the urgent need for treatments that offer a real chance for durable remission. Impressively, 91% of [these] patients in the ZUMA-5 study responded to a single infusion of axicabtagene ciloleucel, including an estimated 74% of patients in a continued remission at 18 months, giving these patients much-needed hope and oncologists an important addition to the treatment armamentarium.”

The single-arm, open-label, multicenter trial enrolled 146 patients with either relapsed or refractory follicular lymphoma and marginal zone lymphoma who had previously received 2 or more lines of systemic therapy, including treatment with an anti-CD20 monoclonal antibody and an alkylating agent. To be eligible for enrollment, patients had to have an ECOG performance status of 0 or 1. Participants underwent leukapheresis and received conditioning chemotherapy followed by an infusion of axi-cel at 2 × 106 CAR T-cells/kg.

The primary end point of the trial was objective response rate (ORR) per central review, while secondary end points comprised DOR, progression-free survival (PFS), overall survival (OS), safety, and blood levels of cytokines and CAR T-cells.

Additional results showed that of 25 patients who experienced a partial remission, 13 met imaging criteria for a CR without confirmation by negative bone marrow biopsy following treatment.

Data from a safety analysis performed in 146 patients showed that grade 3 or higher cytokine release syndrome (CRS) was reported in 8% of patients, while grade 3 or higher neurologic toxicities were reported in 21%. The median time to onset of these effects was 4 days (range, 1-20 days) and 6 days (range, 1-79), respectively. The most frequently reported toxicities that were grade 3 or higher in severity were febrile neutropenia, encephalopathy, and infections with unspecified pathogens.

Axi-cel has also been approved by the FDA as a treatment for adult patients with relapsed or refractory large B-cell lymphoma based on findings from the phase 2 ZUMA-1 trial (NCT02348216).2 The agent is indicated specifically following 2 prior therapies for those with diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL transformed from follicular lymphoma.


  1. US FDA approves Yescarta for relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. News release. Kite. March 5, 2021. Accessed March 5, 2021. http://bit.ly/3kOyKnb
  2. FDA. FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. FDA website. Published October 18, 2017. fda.gov/news-events/press-announcements/fda-approves-car-t-cell-therapy-treat-adults-certain-types-large-b-cell-lymphoma. Accessed May 30, 2020.
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