FDA Approves Liso-Cel in Marginal Zone Lymphoma After 2 Lines of Therapy

The FDA has approved lisocabtagene maraleucel (liso-cel; Breyanzi) as a treatment for patients with relapsed/refractory marginal zone lymphoma (MZL) who have received at least 2 prior lines of systemic therapy, according to a release from the FDA.¹

The recommended liso-cel dose is 90 to 110 x 10⁶ CAR-positive viable T cells, with a 1:1 ratio of CD4 and CD8 components.

Notably, 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.

Supporting results for the approval, and all other indications, primarily came from the MZL cohort of the open-label phase 2 TRANSCEND FL trial (NCT04245839), which evaluated the efficacy and safety of liso-cel as a treatment in adult patients with relapsed/refractory indolent B-cell non-Hodgkin lymphoma.

Previously, in August 2025, the FDA accepted a supplemental biologics license application and granted priority review to liso-cel in this indication; a Prescription Drug User Fee Act date of December 5, 2025, was set.²

Trial Results

Among all 66 efficacy-evaluable patients with MZL treated with liso-cel, the overall response rate (ORR) in the intention-to-treat population was 84.4% (95% CI, 74.4%-91.7%), with 55.8% (95% CI, 44.1%-67.2%) of patients achieving a complete response (CR) as assessed by an independent review committee per CT. The median duration of response was not reached (95% CI, 25.59-not reached).

With a median follow-up of 21.6 months, the 24-month duration of response rate was 88.6%; with a median follow-up of 23.8 months, the 24-month progression-free survival rate was 85.7%; and with a median follow-up of 24.5 months, the 24-month overall survival rate was 90.4%.³

Per safety, liso-cel demonstrated a consistent safety profile with what has been previously reported, with no new safety signals. Cytokine release syndrome (CRS) occurred in 76% of patients, with grade 3 events occurring in 4% and no grade 4 or 5 events reported. Neurologic events occurred in 33% of patients, with grade 3 events occurring in 4% and no grade 4 or 5 events reported.

Liso-cel was administered to all patients in the trial at a target dose of 100 x 10⁶ CAR-positive viable T cells. It was administered 2 to 7 days after lymphodepleting chemotherapy.

A total of 77 leukapheresed patients were included in the intention-to-treat population; among them, 66 patients had measurable disease per CT scan at baseline, received liso-cel in the intended dose range, and had at least 9 months of follow-up from the date of first response.

Eligible patients enrolled in the trial had relapsed/refractory follicular lymphoma of grade 1, 2, or 3a, or MZL histologically confirmed within 6 months of screening, and had received at least 1 prior therapy, including an anti-CD20 and alkylating agent.⁴ An ECOG performance status of 0 or 1, adequate organ function, and adequate vascular access for a leukapheresis procedure were also required. As specifically noted, patients with MZL were required to have received 2 or more prior lines of systemic therapy or had relapsed after hematopoietic stem cell transplant.

Exclusion criteria included evidence or history of diffuse large B-cell lymphoma and follicular lymphoma, World Health Organization subclassification of duodenal-type follicular lymphoma, central nervous system-only involvement by malignancy, prior CAR T-cell or other genetically modified cell therapy, and active hepatitis B or C.

The primary end point of the trial was the ORR as assessed by PET-CT and/or CT using the Lugano classification. Secondary end points were the CR rate, duration of response, progression-free survival, overall survival, adverse events, pharmacokinetics, and quality of life.

References

1. FDA approves lisocabtagene maraleucel for relapsed or refractory marginal zone lymphoma. News release. FDA. December 4, 2025. Accessed December 4, 2025. https://tinyurl.com/4v2jjr2z
2. Bristol Myers Squibb’s application for Breyanzi (lisocabtagene maraleucel) accepted for priority review by U.S. Food and Drug Administration (FDA) in fifth cancer type for relapsed or refractory marginal zone lymphoma (MZL). News release. Bristol Myers Squibb. August 4, 2025. Accessed December 4, 2025. https://tinyurl.com/mwuk2hst
3. Bristol Myers Squibb presents first data from the marginal zone lymphoma cohort of the Transcend FL trial demonstrating deep and durable responses with Breyanzi (lisocabtagene maraleucel). News release. Bristol Myers Squibb. June 16, 2025. Accessed December 4, 2025. https://tinyurl.com/yzeefphx
4. A study to evaluate the efficacy and safety of JCAR017 in adult subjects with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (NHL) (TRANSCEND FL). ClinicalTrials.gov. Updated November 5, 2025. Accessed December 4, 2025. https://tinyurl.com/msvbsbm2