Welcome back to the D.I.S.C.O., FDA’s Drug Information Soundcast in Clinical Oncology, Burst Edition, brought to you by FDA’s Division of Drug Information in partnership with FDA’s Oncology Center of Excellence. Today we’ll provide a quick update on a recent FDA cancer therapeutic approval.
On April 1, 2022, the FDA approved axicabtagene ciloleucel (brand name Yescarta) for adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy. It is not indicated for the treatment of patients with primary central nervous system lymphoma.
Approval was based on ZUMA-7, a randomized, open-label, multicenter trial in adult patients with primary refractory large B-cell lymphoma or relapse within 12 months following completion of first-line therapy. Patients had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous hematopoietic stem cell transplantation. A total of 359 patients were randomized 1:1 to receive a single infusion of axicabtagene ciloleucel following fludarabine and cyclophosphamide lymphodepleting chemotherapy or to receive second-line standard therapy, consisting of 2 or 3 cycles of chemoimmunotherapy followed by high-dose therapy and autologous hematopoietic stem cell transplantation in patients who attained complete remission or partial remission.
The primary efficacy measure was event-free survival determined by an independent review committee. Event-free survival was significantly longer in the axicabtagene ciloleucel arm with a hazard ratio of 0.40. The estimated 18-month event-free survival rate was 41.5% in the axicabtagene ciloleucel arm and 17% in the standard therapy arm. The estimated median event-free survival was 8.3 months and 2 months, respectively. Of patients randomized to receive standard therapy, 35% received on-protocol autologous hematopoietic stem cell transplantation; lack of response to chemotherapy was the most common reason for not receiving hematopoietic stem cell transplantation. The independent review committee -assessed best objective response rate was statistically significantly higher in the axicabtagene ciloleucel arm compared to the standard therapy arm: 83% vs. 50%, respectively.
The prescribing information for axicabtagene ciloleucel has a boxed warning for cytokine release syndrome and neurologic toxicities. In studies of axicabtagene ciloleucel in patients with non-Hodgkin lymphoma, cytokine release syndrome occurred in 90% and neurologic toxicities occurred in 78%.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
Full prescribing information for these approvals can be found on the web at www.fda.gov/, key word search Approved Cellular and Gene Therapy Products.
Health care professionals should report serious adverse events to FDA’s MedWatch Reporting Program at www.fda.gov/medwatch.
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