On December 4, 2025, the U.S. Food and Drug Administration (FDA) approved the CD19-directed chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (Breyanzi) for the treatment of adult patients with relapsed or refractory marginal zone lymphoma who have received at least two prior lines of therapy.
Efficacy for lisocabtagene maraleucel in this indication was evaluated in the follicular lymphoma/marginal zone lymphoma cohort of the open-label, multicenter, single-arm TRANSCEND trial (ClinicalTrials.gov identifier NCT04245839), which enrolled adults with relapsed or refractory marginal zone lymphoma who had received at least two or more lines of systemic therapy or who had relapsed after hematopoietic stem cell transplant. The trial included patients with an ECOG performance status of 1 or less.
In the study, 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). Efficacy analyses were performed in 77 patients who had undergone leukapheresis (the intention-to-treat population) and in 66 patients who had confirmed measurable disease by computed tomography scan at baseline, received the conforming product in intended dose ranges, and had at least 9 months of follow-up from the date of first response.
The main efficacy outcome measure was overall response rate, defined as the percentage of patients with the best overall response of complete response or partial response per Lugano criteria, and duration of response, as determined by an independent review committee.
The overall response rate in the intention-to-treat population was 84.4% (95% confidence interval [CI] = 74.4%–91.7%), and the complete response rate was 55.8% (95% CI = 44.1%–67.2%). The median duration of response was not reached (95% CI = 25.59 to not reached).
The prescribing information includes warnings and precautions for cytokine release syndrome, neurologic toxicities, hypersensitivity reactions, serious infections, prolonged cytopenias, hypogammaglobulinemia, secondary malignancies, and immune effector cell–associated hemophagocytic lymphohistiocytosis-like syndrome.
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.
The application for lisocabtagene maraleucel was granted a Priority Review designation and the agent received an Orphan Drug designation.
