March 5, 2021 Axicabtagene Ciloleucel FDA Approval for Adult Patients with Relapsed or Refractory Follicular Lymphoma (FL) after two or More Systemic Treatments
March 5, 2021 Axicabtagene Ciloleucel FDA Approval for Adult Patients with Relapsed or Refractory Follicular Lymphoma (FL) after two or More Systemic Treatments
On March 5, 2021, the U.S. Food and Drug Administration (FDA) approved Axicabtagene ciloleucel (Yescarta, Kite Pharma, Inc.) for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.
The approval was based on a single-arm, open-label, multicenter study (ZUMA-5; NCT03105336) that evaluated axicabtagene ciloleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in adult patients with relapsed or refractory FL after two or more lines of systemic therapy, including the combination of an anti-CD20 monoclonal antibody and an alkylating agent. After undergoing lymphodepleting chemotherapy, axicabtagene ciloleucel was administered as a single intravenous infusion.
The main efficacy outcomes, as determined by an independent review committee, were objective response rate (ORR) and duration of response (DoR). In the primary efficacy analysis of 81 patients, the ORR was 91% (95% confidence interval [CI] 83–96), with a complete response (CR) rate of 60%, and a median time to response of 1 month. The median DoR was not reached, and the 1-year ongoing response rate was 76.2% (95% CI 63.9, 84.7). In the study, the ORR for all leukapheresed patients (n = 123) was 89% (95% CI 83–94), with a CR rate of 62%.
The prescribing information for axicabtagene ciloleucel includes a Boxed Warning for cytokine release syndrome (CRS) and neurological toxicities. In the pooled analysis of axicabtagene ciloleucel studies in non-Hodgkin lymphoma (NHL) patients, the incidence of CRS was 88% (≥ Grade 3, 10%), and the incidence of neurological toxicities was 81% (≥ Grade 3, 26%). Common non-laboratory adverse reactions (incidence ≥ 20%) in NHL patients included CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, febrile neutropenia, nausea, infections, decreased appetite, chills, diarrhea, tremor, musculoskeletal pain, cough, hypoxia, constipation, vomiting, arrhythmia, and dizziness.
This indication was approved under accelerated approval based on response rates. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
The application was granted priority review, breakthrough therapy designation, and orphan drug designation.
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