FDA Approves Lisocabtagene Maraleucel for Relapsed or Refractory Mantle Cell Lymphoma

May 30, 2024

The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On May 30, 2024, the Food and Drug Administration approved lisocabtagene maraleucel (Breyanzi, Juno Therapeutics, Inc.) 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).

Full prescribing information for Breyanzi will be posted here.

Efficacy and Safety

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 Bruton tyrosine kinase inhibitor, an alkylating agent, and an anti-CD20 agent. The trial included patients with an ECOG performance status of 1 or less, prior autologous and/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 they were assessed by the investigator to have adequate bone marrow function to receive lymphodepleting chemotherapy.

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 analysis included a total of 68 patients with MCL who received at least 2 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 6 months of follow-up from the date of first response.

The main efficacy outcome measure was overall response rate (ORR), defined as percentage of patients with best overall response (BOR) of either complete response (CR) or partial response (PR) after lisocabtagene maraleucel infusion, as determined by an independent review committee (IRC) using 2014 Lugano classification. Other efficacy measures included complete response rate (CRR) and duration of response (DOR), as determined by 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 (≥ 20%) were cytokine release syndrome (CRS), fatigue, musculoskeletal pain, encephalopathy, edema, headache, and decreased appetite. 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.

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 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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