FDA Approves Liso-Cel as First CAR T for Marginal Zone Lymphoma

The FDA has approved lisocabtagene maraleucel (liso-cel; Breyanzi), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in marginal zone lymphoma (MZL).¹

This regulatory milestone marks a significant step toward expanding the therapeutic landscape for adult patients with relapsed or refractory MZL who have previously received at least 2 lines of systemic therapy. The approval makes liso-cel the first and only CAR T-cell therapy for this patient population, addressing a substantial unmet clinical need.

The approval is supported by compelling data from the primary analysis of the MZL cohort of the TRANSCEND FL trial (NCT04245839), an open-label, global, multicenter phase 2 study. The findings from this trial, presented at the 2025 International Conference on Malignant Lymphoma (ICML), demonstrated deep and durable responses with liso-cel.

Among the 66 efficacy-evaluable patients with relapsed or refractory MZL, the overall response rate (ORR) was 95.5% (95% CI, 87.3%–99.1%; 1-sided P <.0001), with a complete response (CR) rate of 62.1% (95% CI, 49.3%–73.8%; 1-sided P <.0001).³ These high rates of durable responses underscore the potential of this one-time therapy to profoundly improve patient outcomes in a setting where current treatment options often lead to repeated relapses.

Regarding safety, the most frequently observed adverse events (AEs) were cytokine release syndrome (CRS) and neurologic toxicities. In the MZL cohort, CRS was reported in 76% of patients, with 4% experiencing grade 3 events. There were no reported cases of grade 4 or 5 CRS. Neurologic events occurred in 33% of patients, with grade 3 cases reported in 4% of patients. No grade 4 or 5 neurologic events were observed. The safety profile, coupled with recent FDA approvals for streamlined patient monitoring requirements and the removal of the Risk Evaluation and Mitigation Strategy (REMS) program, aims to make this personalized therapy more accessible to eligible patients while upholding safety standards.

About MZL and Liso-Cel

MZL is the third most common subtype of non-Hodgkin lymphoma, accounting for approximately 7% of all cases. It typically affects older adults, with the median age at diagnosis around 67 years.² While MZL is generally considered an indolent or slow-growing disease, patients frequently experience multiple relapses over a period of years, and in some cases, the disease can transform into a more aggressive form, such as diffuse large B-cell lymphoma (DLBCL). For these patients who have exhausted multiple lines of therapy, the prognosis remains challenging, highlighting the urgent need for innovative treatments that can deliver sustained, long-term remission. This approval for liso-cel in MZL represents the fifth cancer type for which the therapy is indicated.

About the TRANSCEND FL Study

The TRANSCEND FL study enrolled patients with grade 1, 2, or 3a relapsed or refractory follicular lymphoma or MZL, an ECOG performance status of 0 or 1, adequate organ function, and adequate vascular access for leukapheresis.⁴ Patients with MZL had to have received 2 or more prior lines of systemic therapy, including 1 anti-CD20 agent and an alkylating agent, or have relapsed disease following hematopoietic stem cell transplant.

REFERENCES

1. FDA approves lisocabtagene maraleucel for relapsed or refractory marginal zone lymphoma. News release. US FDA. December 4, 2025. Accessed December 5, 2025. https://tinyurl.com/55x82nc2

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 November 18, 2025. https://tinyurl.com/4skw5sff

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 November 18, 2025. https://tinyurl.com/3jzm7bex

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 July 30, 2025. Accessed November 18, 2025. https://clinicaltrials.gov/study/NCT04245839