New Lymphoma Indication for CAR T-Cell Therapy Shapes Pipeline

On the back of FDA’s newest authorization of lisocabtagene maraleucel (brand name Breyanzi by Juno Therapeutics), a chimeric antigen receptor T-cell (CAR-T) therapy, to treat marginal zone lymphoma (MZL) in adults, the CAR-T becomes the first of its kind approved in the United States for this indication (1). The approval applies to MZL adult patients who have relapsed or failed at least two prior lines of therapy. This authorization represents a notable development for cell-based treatments, particularly in a cancer type where therapeutic options after relapse remain limited (2).

In announcing the approval on Dec. 4, 2025, Vinay Prasad, MD, chief medical and scientific officer and director of FDA’s Center for Biologics Evaluation and Research (CBER), emphasized its significance. “Today’s approval represents a major advancement in precision medicine, essentially turning the patient’s immune system into a more effective tool to treat MZL,” he said in the agency’s press release (1). “[FDA] continues to optimize its regulatory authority to expand treatment options in the fight against cancer.”

According to FDA, MZL accounts for approximately 7% of B-cell non-Hodgkin lymphoma in the US, with roughly 7460 new cases annually (1). Although considered slow-growing, patient outcomes decline sharply once frontline therapies fail, underscoring the need for durable solutions (3). The introduction of an engineered cell therapy into this space signals a shift toward more individualized approaches in diseases historically managed with conventional treatments (1,2).

What does the clinical evidence suggest about long-term outcomes?

The agency’s decision was supported by an open-label clinical trial conducted at multiple centers. The study enrolled adults with relapsed or refractory MZL who had previously undergone at least two systemic therapies or who relapsed following a hematopoietic stem cell transplant. Participants first completed leukapheresis, the process by which their immune cells were collected to manufacture the therapy. After preparatory chemotherapy, the patients received a single infusion between two and seven days later.

Of the 77 individuals who underwent leukapheresis, 66 received the specified single dose, and, among this group, 95.5% showed a response to treatment while 62.1% achieved a complete response with no detectable disease on imaging, according to FDA (1). The median follow-up time was 21.6 months, and responses were reported as durable over that period. These data contribute to a broader industry discussion about the potential for one-time cell therapies to provide lasting benefit in select lymphomas (4).

“Today’s approval reflects [FDA’s] continuing commitment to advance cell therapies to meet the needs of patients with rare cancers,” said Vijay Kumar, acting director of the Office of Therapeutic Products in CBER in the release (1). “In granting approval, FDA took into consideration the high and durable response rate following a one-time treatment in patients with MZL, almost half of whom had either progression within two years of diagnosis or had refractory disease,” he added, emphasizing the significance of this durability.

What influence may this decision have on future cell therapy development?

The approval of this additional indication in lisocabtagene maraleucel’s arsenal makes a notable impact in the broader cell therapy field. As manufacturing platforms, clinical infrastructure, and regulatory pathways continue to evolve, decisions like this one may shape expectations around durability, patient selection, and scalability. For cell therapy developers, the authorization signals continued regulatory support for advancing engineered immune-cell-based treatments beyond the largest lymphoma subtypes (5).

References

1. FDA. FDA Approves First CAR T-Cell Therapy for Marginal Zone Lymphoma In the US. Press Release. Dec. 4, 2025.
2. Palomba, M. L.; Schuster, S. J.; Karmali, R.; et al. CT-230: Lisocabtagene Maraleucel (liso-cel) in Patients With Relapsed or Refractory (R/R) Marginal Zone Lymphoma (MZL) in the Phase 2 TRANSCEND FL Study. Clin. Lymphoma, Myeloma Leuk. 2025, 25 (Suppl. 1), S1006–S1007. DOI: 10.1016/S2152-2650(25)02763-6
3. Wang, H.; Wan, X.; Zhang, Y.; et al. Advances in the Treatment of Relapsed/Refractory Marginal Zone Lymphoma. Front. Oncol. 2024, 14, 1327309. DOI: 10.3389/fonc.2024.1327309
4. Cappell, K. M.; Kochenderfer, J. N. Long-Term Outcomes Following CAR T Cell Therapy: What We Know So Far. Nat. Rev. Clin. Oncol. 2023, 20 (6), 359–371. DOI: 10.1038/s41571-023-00754-1
5. Britton, K.; Mahat, U.; Richardson, N. C.; et al. FDA Approval Summary: Lisocabtagene Maraleucel for Relapsed or Refractory Follicular Lymphoma. Clin. Cancer Res. 2025, 31 (18), 3830–3833. DOI: 10.1158/1078-0432.CCR-25-1035