Yescarta Second Gene Therapy Approved by FDA and First CAR T-Cell Therapy for Large B-Cell Lymphoma

December 2017, Vol 7, No 12 - FDA Approvals, News & Updates


On October 18, 2017, the FDA approved axicabtagene ciloleucel (Yescarta; Kite Pharma), a CD19-directed genetically modified CAR T-cell immunotherapy, for the treatment, after ≥2 lines of systemic therapies, of adults with several types of relapsed or refractory large B-cell lymphoma, including (1) diffuse large B-cell lymphoma (DLBCL) not otherwise specified, (2) primary mediastinal large B-cell lymphoma, (3) high-grade B-cell lymphoma, and (4) DLBCL arising from follicular lymphoma.

“The approval of Yescarta brings this innovative class of CAR-T cell therapies to an additional group of cancer patients with few other options—those adults with certain types of lymphoma that have not responded to previous treatments,” said Peter Marks, MD, PhD, Director, FDA’s Center for Biologics Evaluation and Research.

“Today marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases. In just several decades, gene therapy has gone from being a promising concept to a practical solution to deadly and largely untreatable forms of cancer,” said FDA Commissioner Scott Gottlieb, MD.

The FDA granted axicabtagene ciloleucel priority review and breakthrough therapy and orphan drug designations for these indications.

The safety and efficacy of axicabtagene ciloleucel were evaluated in a single-arm, open-label, multicenter clinical trial involving 111 adults with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. The primary efficacy end points were complete remission rate and the duration of response, as determined by an independent review committee. Of the 101 patients who received axicabtagene ciloleucel, 51% achieved complete remission and 21% achieved partial remission. The median time to response was 0.9 months (range, 0.8-6.2 months), and the median duration of response was 9.2 months.

Axicabtagene ciloleucel was approved with a Risk Evaluation and Mitigation Strategy, including Elements to Assure Safe Use.

Axicabtagene ciloleucel includes a boxed warning about the risk for cytokine-release syndrome (CRS) and neurologic reactions. The most common (≥10%) grade ≥3 events include febrile neutropenia, fever, CRS, encephalopathy, infections-pathogen unspecified, hypotension, hypoxia, and lung infections.