On May 15, 2024, the U.S. Food and Drug Administration (FDA) granted accelerated approval to lisocabtagene maraleucel (Breyanzi®) for adults with relapsed or refractory follicular lymphoma (FL) who have received two or more prior lines of systemic therapy.

FDA update

Efficacy was evaluated in TRANSCEND-FL (NCT04245839), a phase II, open-label, multicenter, single-arm trial in adults with relapsed or refractory FL who had received 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 2–7 days following the completion of lymphodepleting chemotherapy (fludarabine 30 mg/m2 per day and cyclophosphamide 300 mg/m2 per day concurrently for three 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 nine months of follow up from their first response.

The main efficacy outcome measures were overall response rate (ORR), 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 (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 (95% CI = 18.04, not reached).

The most common nonlaboratory adverse reactions reported in at least 20% of patients were cytokine release syndrome (CRS), headache, musculoskeletal pain, fatigue, constipation, and fever. FDA approved lisocabtagene maraleucel with a risk evaluation and mitigation strategy because of the risk for 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. Full prescribing information for lisocabtagene maraleucel will be posted here

The applicant used the Assessment Aid to facilitate the FDA’s assessment. FDA granted the application priority review and orphan drug designation. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact the Oncology Center of Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.