On March 5, 2021, the FDA approved a new indication for axicabtagene ciloleucel (Yescarta; Kite Pharma), a chimeric antigen receptor (CAR) T-cell therapy, for the treatment of patients with relapsed or refractory follicular lymphoma (FL) who have received ≥2 lines of systemic therapy. The FDA granted this indication a priority review as well as breakthrough therapy and orphan drug designations.
Axicabtagene ciloleucel was the first CAR T-cell therapy to be approved by the FDA when it was approved for large B-cell lymphoma. The new approval makes it the first CAR T-cell therapy for indolent FL.
“For follicular patients in the third line of therapy, the 5-year survival rate is only 20%, highlighting the urgent need for treatments that offer a real chance for durable remission. Impressively, 91% of follicular lymphoma patients in the ZUMA-5 study responded to a single infusion of axicabtagene ciloleucel, including an estimated 74% of patients in a continued remission at 18 months,” said Caron A. Jacobson, MD, MMSc, Medical Director, Immune Effector Cell Therapy Program, Dana-Farber Cancer Institute.
The FDA approval was based on efficacy results from the single-arm, open-label, multicenter ZUMA-5 clinical trial of 146 patients with relapsed or refractory FL who had received ≥2 lines of therapy; 81 of them were evaluable for efficacy. Axicabtagene ciloleucel was administered as a single infusion after lymphodepleting chemotherapy.
The main efficacy measures were overall response rate (ORR) and duration of response (DOR). The ORR in the 81 evaluable patients was 91% (95% confidence interval [CI], 83%-96%), including 60% complete remissions. The median time to response was 1 month, the median DOR was not reached, and the 1-year rate of ongoing remission was 76.2%. In the 146 total study patients, the ORR was 89% (95% CI, 83%-94%), including 62% complete responses.
The most common (≥20%) adverse reactions with axicabtagene ciloleucel in this study were cytokine release syndrome, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, febrile neutropenia, nausea, infection, decreased appetite, chills, diarrhea, tremor, musculoskeletal pain, cough, hypoxia, constipation, vomiting, arrhythmias, and dizziness.