FDA Approves Lisocabtagene Maraleucel for Patients With Relapsed/Refractory Marginal Zone Lymphoma
Key Clinical Summary
- Population and Design: On December 4, 2025, the US FDA approved lisocabtagene maraleucel, a CD19-directed CAR T-cell therapy, for adults with R/R MZL after ≥2 prior systemic therapies based on the TRANSCEND FL-MZL trial (NCT04245839)—an open-label, multicenter, single-arm study in 77 leukapheresed and 66 treated patients.
- Efficacy: ORR 84.4% (95% CI, 74.4–91.7) and CR 55.8% (95% CI, 44.1–67.2) per independent review; median DOR not reached (95% CI, 25.59–NR), indicating durable, deep responses after a single infusion.
- Safety: Administered 2–7 days post–lymphodepleting chemotherapy; label includes precautions for CRS, neurologic events, cytopenias, infections, HLH-like syndrome, and secondary malignancies. Recommended dose: 90–110 × 10⁶ CAR+ T cells (1:1 CD4:CD8 ratio).
On December 4, 2025, the US Food and Drug Administration (FDA) approved lisocabtagene maraleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for adult patients with relapsed/refractory (R/R) marginal zone lymphoma (MZL) who have received at least 2 prior lines of systemic therapy.
Efficacy was based on results from the TRANSCEND FL-MZL trial (NCT04245839), an open-label, multicenter, single-arm trial that enrolled adult patients with R/R MZL who had received tw2o or more prior lines of systemic therapy or had relapsed following hematopoietic stem cell transplant (HSCT). Eligible patients had an ECOG performance status of 0 to 1.
Patients received a single dose of lisocabtagene maraleucel 2 to 7 days after lymphodepleting chemotherapy which consisted of fludarabine 30 mg/m²/day and cyclophosphamide 300 mg/m²/day for 3 consecutive days. The primary efficacy end points were overall response rate (ORR) and duration of response (DOR), as assessed by independent review committee (IRC) using Lugano criteria
Efficacy analyses were conducted in 77 leukapheresed patients (intention-to-treat population) and 66 treated patients who had measurable disease at baseline, received conforming product within the intended dose range, and had at least 9 months of follow-up from first response.
The ORR in the ITT population was 84.4% (95% confidence interval [CI], 74.4 to 91.7), with a complete response rate (CRR) of 55.8% (95% CI, 44.1 to 67.2). The median DOR was not reached (95% CI, 25.59 to not reached).
The recommended dose of lisocabtagene maraleucel is 90 to 110 × 10⁶ CAR-positive viable T cells, administered at a 1:1 ratio of CD4 and CD8 components. The prescribing information includes warnings and precautions for cytokine release syndrome (CRS), neurologic toxicities, hypersensitivity reactions, serious infections, prolonged cytopenias, hypogammaglobulinemia, secondary malignancies, and immune effector cell–associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HLH).
Source:
US Food and Drug Administration. Accessed December 4, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lisocabtagene-maraleucel-relapsed-or-refractory-marginal-zone-lymphoma
