FDA Approves Breyanzi for Relapsed/Refractory Marginal Zone Lymphoma

On December 4, 2025, the FDA granted approval to lisocabtagene maraleucel (liso-cel; Breyanzi; Bristol Myers Squibb) for adult patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have received at least 2 prior lines of systemic therapy. This marks the first—and currently only—CAR T-cell therapy approved for this patient population.^1-3

“The FDA approval of [liso-cel] for relapsed or refractory marginal zone lymphoma further solidifies it as the leading CD19-directed CAR T-cell therapy covering the broadest range of B-cell malignancies. This approval in a fifth cancer type reflects our bold vision to bring the transformational potential of cell therapy to more patients," Lynelle B. Hoch, president, Cell Therapy Organization, Bristol Myers Squibb, said in the news release. “[Liso-cel] is the first and only CAR T-cell therapy approved for this patient population, demonstrating Bristol Myers Squibb’s deep commitment to expanding access and reaching as many patients as possible with this innovative, practice-changing treatment.”

The approval was based on results from the MZL cohort of the global phase 2 trial, TRANSCEND FL (NCT04245839), an open-label, multicenter, single-arm study investigating the efficacy and safety of liso-cel in R/R indolent B-cell non-Hodgkin lymphoma, including both follicular lymphoma and MZL.^1,2

Compelling Efficacy and Durable Responses

In the MZL cohort of TRANSCEND FL, 66 efficacy-evaluable patients with measurable disease at baseline received a single infusion of liso-cel after lymphodepleting chemotherapy (fludarabine + cyclophosphamide) administered 2 to 7 days prior.¹

Results were positive, with an overall response rate (ORR) of about 95.5% and a complete response (CR) rate of 62.1%. At a median follow-up of approximately 21.6 months, the duration of response rate was 88.6%; progression-free survival at 24 months was 85.7%, and overall survival at 24 months was 90.4%.²

The high and sustained response rates from a single infusion underscore the transformative potential of lisocabtagene maraleucel in a disease setting where multiple relapses are common and long-term control is often elusive.

Safety Profile and CAR-T-Cell Therapy Logistics

The safety data from the MZL cohort were consistent with prior experience of liso-cel in other B-cell malignancies, with no new safety signals reported.^1,2

As with other CAR-T-cell therapies, administration begins with leukapheresis to collect the patient’s T cells; these are then genetically engineered to express a CAR targeting CD19, expanded ex vivo, and finally infused back into the patient following lymphodepleting chemotherapy.¹

According to the FDA, the recommended dose of liso-cel is 90 to 110 × 10⁶ CAR-positive viable T cells (with a 1:1 CD4:CD8 ratio).³

Adverse events of special interest, including cytokine release syndrome, neurologic toxicities, prolonged cytopenias, hypogammaglobulinemia, serious infections, hypersensitivity reactions, and immune effector–cell associated syndromes, remain relevant risks and are included in the prescribing information.¹

Implications for MZL Treatment Landscape

MZL constitutes roughly 7% of all non-Hodgkin lymphomas in the United States. While many patients achieve remission with first-line therapy, relapse is common, sometimes occurring multiple times over many years. For patients with multiple relapses or refractory disease, therapeutic options have historically been limited and often only palliative.¹

For pharmacists, hematologists, and oncologists, this expands the armamentarium for MZL, offering hope for prolonged remissions and potential functional cures in a patient population with unmet need. It also underscores the growing role of CAR T-cell therapies beyond aggressive lymphomas and into indolent subtypes, reflecting advances in both efficacy and safety of cellular immunotherapies.

Conclusion

With this approval, attention will likely turn to real-world implementation: identifying eligible patients, establishing CAR-T therapy logistics at treatment centers, ensuring access through payer coverage, and managing postinfusion monitoring and long-term follow-up. The durable responses seen in the clinical trial are promising, but long-term data will continue to accrue.

Pharmacists and clinicians should also stay alert for safety signals as use expands beyond the clinical trial setting, especially given the risks inherent to CAR-T therapies.

REFERENCES

1. Bristol Myers Squibb’s Breyanzi Approved by the U.S. FDA as the First and Only CAR T Cell Therapy for Adults with Relapsed or Refractory Marginal Zone Lymphoma (MZL). Bms.com. Published 2020. Accessed December 5, 2025. https://news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibbs-Breyanzi-Approved-by-the-U-S--FDA-as-the-First-and-Only-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Marginal-Zone-Lymphoma-MZL/default.aspx

2. Clinicaltrials.gov. Updated November 5, 2025. Accessed December 5, 2025. https://clinicaltrials.gov/study/NCT04245839

3. Center. lisocabtagene maraleucel. U.S. Food and Drug Administration. Updated December 4, 2025. Accessed December 5, 2025 https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/breyanzi