FDA Approves Axicabtagene Ciloleucel for Large B-Cell Lymphoma

On October 18, 2017, the U.S. Food and Drug Administration (FDA) granted regular approval to axicabtagene ciloleucel (Yescarta) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two 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.

Axicabtagene ciloleucel is a chimeric antigen receptor (CAR) T-cell immunotherapy.  It consists of autologous T cells that are genetically modified to produce a CAR protein, allowing the T cells to identify and eliminate CD19–expressing normal and malignant cells.

Trial Results

Approval was based on a single-arm multicenter trial of 108 adult patients with aggressive B-cell non-Hodgkin lymphoma. Eligible patients had refractory disease to the most recent therapy or relapse within 1 year after autologous hematopoietic stem cell transplantation. Patients received a single infusion of axicabtagene ciloleucel following completion of lymphodepleting chemotherapy.

Of the 101 patients evaluated for efficacy, the objective response rate as assessed by independent central review was 72%, with a complete remission rate of 51% (95% confidence interval [CI] = 41–62). The duration of response was longer in patients with a best overall response of complete response, as compared to a best overall response of partial remission. Among patients achieving a complete response, the estimated median duration of response was not reached (95% CI = 8.1 months to not estimable) after a median follow-up of 7.9 months. The estimated median duration of response among patients in partial remission was 2.1 months (95% CI = 1.3–5.3).

The most common grade 3 or higher adverse reactions (incidence of 10% or greater) include febrile neutropenia, fever, cytokine-release syndrome, encephalopathy, infections, hypotension, and hypoxia. Serious adverse reactions occurred in 52% of patients and included cytokine-release syndrome, neurologic toxicity, prolonged cytopenias (including neutropenia, thrombocytopenia, and anemia), and serious infections. Fatal cases of cytokine-release syndrome and neurologic toxicity occurred.

The FDA approved axicabtagene ciloleucel with a Risk Evaluation and Mitigation Strategy.

The recommended dose of axicabtagene ciloleucel is a single intravenous infusion with a target of 2 × 106 CAR-positive viable T cells per kg body weight (maximum 2 × 108), preceded by fludarabine and cyclophosphamide lymphodepleting chemotherapy. 

Axicabtagene ciloleucel is not indicated for the treatment of patients with primary central nervous system lymphoma.

Full prescribing information is available at: https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm581222.htm.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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