FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma
On May 15, 2024, the Food and Drug Administration granted accelerated approval to lisocabtagene maraleucel (Breyanzi, Juno Therapeutics, Inc.) for adults with relapsed or refractory follicular lymphoma (FL) who have received two or more prior lines of systemic therapy.
Full prescribing information for Breyanzi will be posted here.
Efficacy and Safety
Efficacy was evaluated in TRANSCEND-FL (NCT04245839), a Phase 2, open-label, multicenter, single-arm trial in adults with relapsed or refractory FL 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 ECOG 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, following the completion of lymphodepleting chemotherapy (fludarabine 30 mg/m2/day and cyclophosphamide 300 mg/m2/day concurrently for 3 days.) The primary efficacy population included 94 patients with PET-positive disease at baseline or after bridging therapy, 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 (ORR), defined as the percentage of patients with a best overall response (BOR) of complete response or partial response after lisocabtagene maraleucel infusion, and duration of response (DOR) as determined by an independent review committee. The ORR was 95.7% (95% CI: 89.5, 98.8). After a median follow up of 16.8 months (95% CI: 16.3, 17.0), the median DOR was not reached (NR) (95% CI: 18.04, NR).
The most common nonlaboratory adverse reactions (≥20%) were cytokine release syndrome (CRS), headache, musculoskeletal pain, fatigue, constipation, and fever. FDA approved lisocabtagene maraleucel with a Risk Evaluation and Mitigation Strategy due to the risk of fatal or life-threatening CRS 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.
Expedited Programs
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. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
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