Lisocabtagene Maraleucel Approved for Relapsed or Refractory Marginal Zone Lymphoma
Expert Perspectives · Lyn Brook · 2025-12-18
The FDA has approved the CD19‑directed CAR T‑cell therapy lisocabtagene maraleucel (Breyanzi®, Juno Therapeutics, a Bristol Myers Squibb Company) for adults with relapsed or refractory marginal zone lymphoma (MZL) who have received at least two prior lines of systemic therapy.
Why This Approval Matters
Marginal zone lymphoma is an indolent B‑cell non‑Hodgkin lymphoma that frequently relapses, and responses to subsequent lines of systemic therapy often diminish over time. Patients who have received multiple prior regimens or relapsed after hematopoietic stem cell transplant (HSCT) have limited curative options. The approval of lisocabtagene maraleucel offers a one‑time, personalized cellular immunotherapy with high overall and complete response rates and durable remissions in a population with heavily pretreated, relapsed or refractory disease.
Breaking Down TRANSCEND FL‑MZL
Efficacy was studied in the TRANSCEND FL‑MZL Cohort (NCT04245839), a phase 2, open‑label, multicenter, single‑arm trial in adults with relapsed or refractory MZL who had received at least two prior systemic regimens or had relapsed following HSCT. All enrolled patients had an ECOG performance status of 0-1.
Patients underwent leukapheresis and then received lymphodepleting chemotherapy with fludarabine 30 mg/m²/day and cyclophosphamide 300 mg/m²/day, administered concurrently for three days, followed by a single infusion of lisocabtagene maraleucel two to seven days after completion of lymphodepletion.
Efficacy analyses included:
- 77 leukapheresed patients (intention‑to‑treat population)
- 66 treated patients who met key criteria (confirmed measurable disease by CT at baseline, received conforming product within the intended dose range, and had ≥9 months of follow‑up from first response)
The primary efficacy end point was overall response rate (ORR), defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) per Lugano criteria, with duration of response (DOR) assessed by an independent review committee.
In the ITT population:
- ORR was 84.4%
- CR rate was 55.8%
- Median DOR was not reached, indicating sustained remissions among responders at the time of analysis.
Managing Adverse Events
The prescribing information for lisocabtagene maraleucel includes important warnings and precautions typical of CD19‑directed CAR T‑cell products, including:
- Cytokine release syndrome (CRS)
- Neurologic toxicities (immune effector cell–associated neurotoxicity)
- Hypersensitivity reactions
- Serious infections
- Prolonged cytopenias
- Hypogammaglobulinemia
- Secondary malignancies
- Immune effector cell–associated hemophagocytic lymphohistiocytosis (HLH)–like syndrome
Dosing and Administration
The recommended dosage of lisocabtagene maraleucel is 90 to 110 × 10⁶ CAR‑positive viable T cells, administered as a defined composition with a 1:1 ratio of CD4 and CD8 cell components.
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