FDA Accepts Breyanzi sBLA from Bristol Myers Squibb and Grants It Priority Review for MZL

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Bristol Myers Squibb announced on Aug. 4, 2025 that FDA has accepted the supplemental biologics license application (sBLA) for lisocabtagene maraleucel, or liso-cel (brand name Breyanzi), a chimeric antigen receptor T-cell (CAR-T) cell therapy. The company is seeking approval for the potential treatment of adults with relapsed or refractory marginal zone lymphoma (MZL) who have received at least two prior lines of systemic therapy.

FDA has also granted the application priority review and has assigned a Prescription Drug User Fee Act goal date of Dec. 5, 2025. If approved, liso-cel has the potential to be the first and only CAR-T cell therapy approved for MZL, which would be the fifth cancer type for which the therapy would be approved (1).

“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 Rosanna Ricafort, vice-president, Senior Global Program Lead for Hematology and Cell Therapy, Bristol Myers Squibb, in a company press release (1).

The company’s progress in drug development builds on its continued efforts to collaborate across the healthcare ecosystem, with an ultimate goal of reaching more patients and democratizing access to cell therapy. FDA approved streamlined patient monitoring requirements as well as the removal of the Risk Evaluation and Mitigation Strategies (2) program for Bristol Myers Squibb’s liso-cel (Breyanzi) to ease known barriers to treatment and administration while maintaining patient safety.

“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,” said Ricafort in the release.

What is MZL?

MZL is the third most common lymphoma and accounts for approximately 7% of all non-Hodgkin lymphoma cases (3). The median age for most patients with MZL is 67 years when diagnosed (3). This type of cancer develops when white blood cells cluster together and form lumps in the lymph nodes or organs. Initial therapy has shown to lead to remission; however, relapse is common and can sometimes occur several times over many years. Additionally, a few cases of MZL can transform into diffuse large-B-cell lymphoma (DLBCL), which is a more aggressive lymphoma (1).

What is liso-cel?

Liso-cel (Breyanzi) is a CD19-directed CAR-T cell therapy that contains a 4-1BB costimulatory domain. This domain enhances the ability of the CAR-T cells to expand and persist. The therapy is made from a patient’s own T cells that are collected and genetically reengineered into CAR-T cells. The therapy is administered back to the patient by intravenous infusion as a one-time treatment. The overall treatment process comprises blood collection, CAR T-cell creation, potential bridging therapy, lymphodepletion, administration, and side-effect monitoring.

Liso-cel (under the brand name Breyanzi) is currently approved in the United States for the following indications:

• adult patients with large B-cell lymphoma, including DLBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have either/or:
  • refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy
  • refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and who are not eligible for hematopoietic stem cell transplantation due to comorbidities or age
  • relapsed or refractory disease after two or more lines of systemic therapy
• adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 inhibitor
• adult patients with relapsed or refractory follicular lymphoma who have received two or more prior lines of systemic therapy
• adult patients with relapsed or refractory mantle cell lymphoma who have received at least two prior lines of systemic therapy, including a BTK inhibitor.

In addition to the US, liso-cel (Breyanzi) is approved in Japan, the European Union, Switzerland, the United Kingdom, and Canada.

References

1. Bristol Myers Squibb. Bristol Myers Squibb’s Application for Breyanzi (lisocabtagene maraleucel) Accepted for Priority Review by US Food and Drug Administration (FDA) in Fifth Cancer Type for Relapsed or Refractory Marginal Zone Lymphoma (MZL). Press Release. Aug. 4, 2025.
2. FDA. Risk Evaluation and Mitigation Strategies | REMS. fda.gov, last updated May 5, 2025 (accessed Aug. 6, 2025).
3. Cheah, C. Y.; Zucca, E.; Rossi, D.; Habermann, T. M. Marginal Zone Lymphoma: Present Status and Future Perspectives. Haematologica 2022, 107 (1). DOI: 10.3324/haematol.2021.278755