On May 30, 2024, the U.S. Food and Drug Administration approved lisocabtagene maraleucel (Breyanzi®) for adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase inhibitor (BTKi).

FDA update

Efficacy was evaluated in TRANSCEND-MCL (NCT02631044), an open-label, multicenter, single-arm trial in adult patients with relapsed or refractory MCL who had received at least two prior lines of therapy, including a BTKi, an alkylating agent, and an anti-CD20 agent. The trial included patients with an ECOG performance status of 1 or less, prior autologous or allogeneic hematopoietic stem cell transplantation, and secondary central nervous system lymphoma involvement. There was no prespecified threshold for blood counts; patients were eligible to enroll if the investigator determined they had adequate bone marrow function to receive lymphodepleting chemotherapy.

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 3 days).

The primary efficacy analysis was conducted with 68 patients with MCL who received at least two prior lines of therapy including a BTKi, had PET-positive disease at study baseline or after bridging therapy, received conforming product in the intended dose range, and had at least six months of follow-up from the date of first response. The main efficacy outcome measure was overall response rate (ORR), defined as the percentage of patients with a best overall response (either complete or partial response) after lisocabtagene maraleucel infusion, as determined by an independent review committee (IRC) using 2014 Lugano classification. Other efficacy measures were complete response rate (CRR) and duration of response (DOR), as determined by the IRC. The ORR was 85.3% (95% CI = 74.6, 92.7) and the CRR was 67.6% (95% CI = 55.2, 78.5). After a median follow-up of 22.2 months (95% CI = 16.7, 22.8), the median DOR was 13.3 months (95% CI = 6.0, 23.3).

The most common nonlaboratory adverse reactions reported in at least 20% of patients were cytokine release syndrome (CRS), fatigue, musculoskeletal pain, encephalopathy, edema, headache, and decreased appetite. FDA’s approval of lisocabtagene maraleucel includes 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 90–110 × 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 FDA’s review. 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 regulated by the Center for Biologics Evaluation and Research, healthcare professionals may email OTPRPMS@fda.hhs.gov.