On May 15, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (Breyanzi) for adult patients with relapsed or refractory follicular lymphoma who have received two or more prior lines of systemic therapy.
TRANSCEND-FL
Efficacy was evaluated in TRANSCEND-FL (ClinicalTrials.gov identifier NCT04245839), a phase II, open-label, multicenter, single-arm trial in adults with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy, including an anti-CD20 antibody and an alkylating agent. Patients were eligible to enroll in the study if they had adequate bone marrow function to receive lymphodepleting chemotherapy and an Eastern Cooperative Oncology Group performance status of 1 or less.
Following apheresis and prior to lymphodepletion and subsequent administration of lisocabtagene maraleucel, patients could receive bridging therapy for disease control. Patients received a single dose of lisocabtagene maraleucel 2 to 7 days after the completion of lymphodepleting chemotherapy (fludarabine at 30 mg/m2/d and cyclophosphamide at 300 mg/m2/d concurrently for 3 days.) The primary efficacy population included 94 patients with positron-emission tomography–positive disease at baseline or after bridging therapy, who received conforming product in the intended dose range, and had at least 9 months of follow-up from first response.
The main efficacy outcome measures were overall response rate (defined as the percentage of patients with a best overall response of complete response or partial response after lisocabtagene maraleucel infusion) and duration of response as determined by an independent review committee. The overall response rate was 95.7% (95% confidence interval [CI] = 89.5%–98.8%). After a median follow-up of 16.8 months (95% CI = 16.3–17.0 months), the median duration of response was not reached (95% CI = 18.04 months to not reached).
The most common nonlaboratory adverse reactions (occurring in ≥ 20% of patients who received lisocabtagene maraleucel) were cytokine-release syndrome, headache, musculoskeletal pain, fatigue, constipation, and fever. The FDA approved lisocabtagene maraleucel with a Risk Evaluation and Mitigation Strategy due to the risk of fatal or life-threatening cytokine-release syndrome and neurologic toxicities.
The recommended lisocabtagene maraleucel dose is 90 to 110 × 106 CAR-positive viable T cells with a 1:1 ratio of CD4 and CD8 components.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review and Orphan Drug designation.
