On March 5, the U.S. Food and Drug Administration (FDA) granted accelerated approval to axicabtagene ciloleucel (Yescarta) for adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.
Approval in follicular lymphoma was based on a single-arm, open-label, multicenter trial (ZUMA-5; ClinicalTrials.gov identifier NCT03105336) that evaluated axicabtagene ciloleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy, including the combination of an anti-CD20 monoclonal antibody and an alkylating agent. Following lymphodepleting chemotherapy, axicabtagene ciloleucel was administered as a single intravenous infusion.
The main efficacy measures were objective response rate and duration of response as determined by an independent review committee. Among 81 patients in the primary efficacy analysis, the objective response rate was 91% (95% confidence interval [CI] = 83%–96%) with a complete remission rate of 60% and a median time to response of 1 month. The median duration of response was not reached, and the 1-year rate of continued remission was 76.2% (95% CI = 63.9%–84.7%). For all leukapheresed patients in this trial (n = 123), the objective response rate was 89% (95% CI = 83%–94%), with a complete remission rate of 62%.
The prescribing information for axicabtagene ciloleucel has a boxed warning for cytokine-release syndrome and neurologic toxicities. In studies of axicabtagene ciloleucel among all patients with non-Hodgkin lymphoma, cytokine-release syndrome occurred in 88% (grade ≥ 3, 10%) and neurologic toxicities occurred in 81% (grade ≥ 3, 26%). The most common nonlaboratory adverse reactions (incidence ≥ 20%) in patients with non-Hodgkin lymphoma are cytokine-release syndrome, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, febrile neutropenia, nausea, infections with pathogen unspecified, decreased appetite, chills, diarrhea, tremor, musculoskeletal pain, cough, hypoxia, constipation, vomiting, arrhythmia, and dizziness.