FDA Approves Axicabtagene Ciloleucel for Relapsed/Refractory Follicular Lymphoma

Follicular lymphoma cells.

The FDA has granted accelerated approval to axicabtagene ciloleucel (Yescarta®, Kite Pharma, Inc.) for adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy, including the combination of an anti-CD20 monoclonal antibody and an alkylating agent. An indolent form of non-Hodgkin lymphoma (NHL) that is not generally curable, FL is considered a chronic disease. Therefore, people living with FL often require second-line therapies after their disease relapses or becomes refractory.

According to 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, “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 five-year survival rate is only 20%, highlighting the urgent need for treatments that offer a real chance for durable remission.”

Axicabtagene ciloleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, was previously approved in 2017 for relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. The latest approval for FL was granted based on the high response rate seen in ZUMA-5 (NCT03105336), a phase 2 trial, results of which were presented at the 2020 American Society of Hematology (ASH) annual meeting. The trial enrolled 124 patients with FL to receive a single infusion of axicabtagene ciloleucel at 2×106 CAR T cells/kg following leukapheresis and conditioning therapy with cyclophosphamide/fludarabine. Patients had a median of three prior lines of therapy. The primary end point was objective response rate; secondary endpoints included duration of response and complete response.

Among the 81 patients with FL in the primary efficacy analysis, the objective response rate was 91%, with a complete remission rate of 60%. The median time to response was one month, and the median duration of response has not yet been reached. Among the total population of 123 patients with FL who underwent leukapheresis, axicabtagene ciloleucel produced an objective response rate of 89% and a complete remission rate of 62%.

Studies of axicabtagene ciloleucel in patients with NHL have demonstrated that cytokine release syndrome occurs in 88% (grade ≥3, 10%) and neurologic toxicities occur in 81% (grade ≥3, 26%); the prescribing information for axicabtagene ciloleucel contains a boxed warning for both of these. Other common adverse reactions occurring in at least 20% of patients included fever, hypotension, encephalopathy, tachycardia, fatigue, headache, febrile neutropenia, nausea, infections, decreased appetite, chills, diarrhea, tremor, musculoskeletal pain, cough, hypoxia, constipation, vomiting, arrhythmias, and dizziness.

Dr. Jacobson, who presented the data at the ASH annual meeting, commented, “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.”

For More Information

Jacobson C, Chavez JC, Sehgal AR, et al (2020). Primary analysis of Zuma-5: a phase 2 study of axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). Blood (ASH Annual Meeting Abstracts), 136(suppl_1):40-41. DOI:10.1182/blood-2020-136834

Clinicaltrials.gov (2021). A phase 2 multicenter study of axicabtagene ciloleucel in subjects with relapsed/refractory indolent non-Hodgkin lymphoma (Zuma-5). NLM identifier: NCT03105336.

Yescarta® (axicabtagene ciloleucel) prescribing information (2020). Kite Pharma. Available at https://www.fda.gov/media/108377/download

US Food & Drug Administration (2021). FDA grants accelerated approval to axicabtagene ciloleucel for relapsed or refractory follicular lymphoma [news release]. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-axicabtagene-ciloleucel-relapsed-or-refractory-follicular-lymphoma?utm_medium=email&utm_source=govdelivery

Image credit: Ed Uthman. Licensed under CC BY-SA 2.0

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