On December 4, 2025, the U.S. Food and Drug Administration approved lisocabtagene maraleucel (Breyanzi) for adults with relapsed or refractory marginal zone lymphoma (MZL) who have received at least two prior lines of systemic therapy. This approval offers an important new CAR-T option for a population with limited salvage treatments.
Clinical Trial Basis — TRANSCEND FL-MZL
The approval is based on results from the TRANSCEND FL-MZL Cohort (NCT04245839), an open-label, multicenter, single-arm trial enrolling adults with R/R MZL, including those who relapsed post-hematopoietic stem cell transplantation. Enrollment required an ECOG performance status of 0–1, reflecting a relatively fit population for CAR-T therapy.
Participants received lymphodepleting chemotherapy prior to infusion:
Fludarabine 30 mg/m²/day + Cyclophosphamide 300 mg/m²/day for 3 consecutive days,
followed 2–7 days later by a single infusion of lisocabtagene maraleucel.
Regimen and Dosing
Breyanzi is an autologous CD19-directed CAR-T therapy composed of CD4 and CD8 T cells in a 1:1 ratio.
Recommended dose:
→ 90–110 × 10⁶ CAR-positive viable T cells,
administered once, after completion of lymphodepletion.
Patients are monitored per CAR-T safety guidelines, and hospitalization/close observation is recommended as per REMS-style programs for CRS and neurotoxicity monitoring.
Efficacy Outcomes
Among 77 leukapheresed patients (ITT population):
- Overall response rate (ORR): 84.4% (95% CI: 74.4–91.7)
- Complete response rate (CRR): 55.8% (95% CI: 44.1–67.2)
- Median duration of response: Not reached, suggesting durable benefit
These results indicate robust and sustained remission potential in heavily pre-treated R/R MZL.
Safety Profile
Toxicities were consistent with CAR-T therapy expectations. The prescribing information includes warnings for:
- Cytokine release syndrome (CRS)
- Neurologic toxicities/ICANS
- Serious infections
- Prolonged cytopenias & hypogammaglobulinemia
- Secondary malignancies
- Immune-effector-cell–associated HLH-like syndrome
Patients require monitoring in centers experienced with CAR-T management.