FDA Grants Priority Review to Liso-Cel for R/R Marginal Zone Lymphoma

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The FDA has granted priority review to a supplemental biologics license application (sBLA) seeking the approval of lisocabtagene maraleucel (liso-cel; Breyanzi) for the treatment of adult patients with relapsed/refractory marginal zone lymphoma (MZL) who have received at least 2 prior lines of systemic therapy.1

The sBLA is supported by data from the MZL cohort of the phase 2 TRANSCEND FL trial (NCT04245839). Data from this cohort presented at the 2025 International Conference on Malignant Lymphoma showed that efficacy-evaluable patients (n = 66) achieved an overall response rate (ORR) of 95.5% (95% CI, 87.3%-99.1%; 1-sided P < .0001), which included a complete response (CR) rate of 62.1% (95% CI, 49.3%-73.8%; 1-sided P < .0001).2 The 24-month duration of response (DOR) rate was 88.6% at a median follow-up of 21.6 months; the 24-month progression-free survival (PFS) rate was 85.7% at a median follow-up of 23.8 months; and the 24-month overall survival (OS) rate was 90.4% at a median follow-up of 24.5 months.

“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,” Rosanna Ricafort, vice president and senior global program lead for Hematology and Cell Therapy at Bristol Myers Squibb, stated in a news release.1 “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.”

TRANSCEND FL Overview

The open-label, global, multicenter trial evaluated liso-cel in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Notably, prior data from the study supported the May 2024 accelerated approval of liso-cel for the treatment of adult patients with relapsed/refractory follicular lymphoma who have received 2 or more prior lines of systemic therapy.3

To enroll, patients needed to be at least 18 years of age with relapsed/refractory grade 1, 2, or 3a follicular lymphoma; or relapsed/refractory MZL.4 At least 1 prior line of therapy featuring an anti-CD20 therapy and an alkylating agent was required for all patients. Those with MZL were required to have at least 2 prior lines of therapy or relapsed disease following hematopoietic stem cell transplant. Other key inclusion criteria comprised an ECOG performance status of 0 or 1 and adequate organ function.

Investigators excluded patients with evidence or a history of composite diffuse large B-cell lymphoma and follicular lymphoma, or of transformed follicular lymphoma; those with a WHO subclassification of duodenal-type follicular lymphoma; and those with central nervous system–only involvement. Prior CAR T-cell therapies or other genetically modified cellular therapies were also not allowed.

After undergoing leukapheresis, patients received lymphodepleting chemotherapy consisting of fludarabine at 30 mg/m2 per day and cyclophosphamide at 300 mg/m2 per day for 3 days. Liso-cel was then infused on day 1 at a target dose of 100 x 106 CAR-positive T cells.

Along with the primary end point of ORR, secondary end points comprised CR rate, DOR, PFS, OS, safety, and pharmacokinetics.

Safety Info

Data from TRANSCEND FL showed that no new safety signals were reported in the MZL cohort. Any-grade cytokine release syndrome (CRS) was reported in 76% of patients, including 4% who had grade 3 CRS. No instances of grade 4/5 CRS occurred.2

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://news.bms.com/news/details/2025/Bristol-Myers-Squibbs-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/default.aspx
  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 4, 2025. https://news.bms.com/news/corporate-financial/2025/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/default.aspx
  3. FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma. FDA. May 15, 2024. Accessed August 4, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma
  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 August 4, 2025. https://clinicaltrials.gov/study/NCT04245839

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