FDA Approves Axi-Cel for Relapsed/Refractory Follicular Lymphoma in Third-Line or Beyond


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

The FDA has granted an accelerated approval to axicabtagene ciloleucel (axi-cel; Yescarta) for the treatment of adult patients with relapsed or refractory follicular lymphoma who have received 2 or more prior lines of systemic therapy.1

This approval marks the first for a chimeric antigen receptor (CAR) T-cell therapy for patients with indolent follicular lymphoma.

“Once a follicular lymphoma patient’s disease relapses, the duration of response to care shortens with each round of therapy. Additionally, for follicular patients 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,” said Caron A. Jacobson, MD, MMSc, medical director, Immune Effector Cell Therapy Program, Dana-Farber Cancer Institute and assistant professor of medicine, Harvard Medical School, in a statement.

Approval was granted based on findings from the follicular lymphoma cohort of the multicenter, single-arm, phase 2 ZUMA-5 trial (NCT03105336), which demonstrated a high response rate for patients with relapsed or refractory follicular lymphoma treated with the autologous anti-CD19 CAR T-cell therapy (n = 81).

In this cohort, the response rate was 91% with 74% still in response at 18 months. At a median follow-up of 14.5 months, the median duration of response was not yet reached.

Among 146 patients in the safety analysis set, cytokine release syndrome (CRS) of grade ≥3 was only reported in 8% of patients and grade ≥3 neurologic toxicities were reported in 21%.

“Impressively, 91% of follicular lymphoma 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,” added Jacobson.

In findings from the trial presented at the 2020 American Society of Hematology Annual Meeting, the follicular lymphoma cohort had an objective response rate of 94% with complete responses in 80% and partial responses in 14%. An additional 4% of patients had stable disease and 2% of patients had undefined response.2

At 1 year, the duration of response rate was 77.0% and 64% of patients had an ongoing response, including in 78% who had a complete response and 17% who had a partial response.

The study enrolled 151 patients with relapsed or refractory indolent non-Hodgkin lymphoma, either follicular lymphoma or marginal zone lymphoma who had received 2 or more prior lines of therapy. The follicular lymphoma cohort was required to have grade 1 to 3A disease. Prior treatment was required to include an anti-CD20 monoclonal antibody and an alkylating agent.

Prior to receiving the CAR T cells, patients in the trial underwent conditioning therapy with fludarabine and cyclophosphamide as well as leukapheresis. Axi-cel was administered at 2 x 106 CAR+ cells/kg.

In the overall population, grade ≥3 adverse effects occurred in 86% of patients, the most common of which were cytopenias (70%) and infections (16%). Three deaths were reported: 1 that was related to axi-cel due to multisystem organ failure in the context of CRS, while the other 2 were unrelated to study treatment and were due to aortic dissection and coccidioidomycosis.

Axi-cel was first approved in October 2017 for the treatment of adult patients with certain types of large B-cell lymphoma who have not responded to or who have relapsed after at least 2 other types of treatment.


U.S. 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 6, 2021. https://bit.ly/30jVwtK

Jacobson C, Chavez JC, Sehgal A, et al. Primary analysis of ZUMA-5: a phase 2 study of axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory indolent non-Hodgkin lymphoma. Presented at: 2020 ASH Annual Meeting & Exposition; December 4-8, 2020; Virtual. Abstract 700.

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