FDA Fast-Tracks Breyanzi as First CAR T Cell Therapy for Marginal Zone Lymphoma

The U.S. Food and Drug Administration (FDA) has accepted Bristol Myers Squibb’s Priority Review application for Breyanzi® (lisocabtagene maraleucel) as a potential first-in-class CAR T cell therapy for relapsed or refractory marginal zone lymphoma (MZL). Backed by data from the Phase 2 TRANSCEND FL trial showing high, durable responses and a consistent safety profile, Breyanzi could address a critical treatment gap in MZL.

The application, which carries a Prescription Drug User Fee Act (PDUFA) action date in December 2025, is based on findings recently presented during an oral session at the 2025 International Conference on Malignant Lymphoma (ICML), underscoring the clinical promise of this personalized cell therapy.

Addressing a High-Unmet-Need Population

MZL, an indolent but often relapsing B-cell non-Hodgkin lymphoma, accounts for approximately 7% of all NHL cases. Although frontline therapies often induce remission, most patients—diagnosed around age 67—face repeated relapses over time. For those who have undergone two or more lines of systemic therapy, treatment options remain limited and largely palliative.

“While initial therapy for MZL can be effective, multiple relapses over the course of several years are common, leaving patients in need of a new treatment option that can provide high, lasting response rates,” said Dr. Rosanna Ricafort, VP, Senior Global Program Lead for Hematology and Cell Therapy at BMS. “This FDA acceptance brings us one step closer to potentially standardizing CAR T cell therapy as a treatment option for MZL, while building on our commitment to bring this personalized therapy to as many eligible patients as possible.”

Targeting Indolent NHL Subtypes

TRANSCEND FL (NCT04245839) is a global, multicenter, open-label Phase 2 trial evaluating the efficacy and safety of Breyanzi in relapsed or refractory indolent B-cell lymphomas, including both follicular lymphoma (FL) and MZL. While the overall response rate serves as the primary endpoint, the trial also examines complete response rate, duration of response, and progression-free survival as key secondary measures.

Although detailed subgroup results from the MZL cohort have yet to be published in a peer-reviewed journal, data presented at ICML 2025 showed that Bre

yanzi achieved meaningful and durable responses, with safety consistent with previous findings in other lymphoma subtypes.

Expanding the Reach of CAR T Cell Therapy

Breyanzi is a CD19-directed CAR T cell therapy that uses a 4-1BB costimulatory domain to enhance CAR T cell expansion and persistence. Manufactured from a patient’s own T cells, the therapy involves genetic modification and re-infusion as a one-time treatment. It is already approved for several relapsed or refractory lymphomas, including large B-cell lymphoma (LBCL), follicular lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma.

Importantly, the FDA recently approved revisions that streamline patient monitoring and eliminated the Risk Evaluation and Mitigation Strategy (REMS) program for Breyanzi, potentially improving access by reducing logistical hurdles and easing treatment administration.