FDA Grants Priority Review for Liso-Cel in Marginal Zone Lymphoma

The US FDA has accepted for priority review the supplemental biologics license application (sBLA) for lisocabtagene maraleucel (liso-cel; Breyanzi), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in marginal zone lymphoma (MZL).¹ The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of December 5, 2025.

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. This application, if approved, would make liso-cel the first and only CAR T-cell therapy for this patient population, addressing a substantial unmet clinical need.

“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 press release. “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.”

The sBLA 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, which were 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).² 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.¹ 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. The potential approval for liso-cel in MZL would represent 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 or 1, adequate organ function, and adequate vascular access for leuakpheresis.³ 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.

The study is currently recruiting patients across 59 sites in the US, Austria, Canada, France, Germany, Italy, Japan, Spain, Sweden, and the United Kingdom.

REFERENCES:

1. 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 August 5, 2025. https://tinyurl.com/4skw5sff

2. 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 August 5, 2025. https://tinyurl.com/3jzm7bex

3. 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 August 5, 2025. https://clinicaltrials.gov/study/NCT04245839