FDA Approves Liso-Cel in Pretreated R/R Marginal Zone Lymphoma

The FDA has approved lisocabtagene maraleucel (liso-cel; Breyanzi) for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) following at least 2 prior lines of therapy.¹

The approval is supported by data from the open-label, multicenter, single-arm phase 2 TRANSCEND FL-MZL trial (NCT04245839), which evaluated its use in patients with relapsed/refractory MZL who had received 2 or more lines of prior therapy following hematopoietic stem cell transplant (HSCT), including patients with an ECOG score of 1 or less.

The overall response rate (ORR) in the intent-to-treat population was 84.4% (95% CI, 74.4%-91.7%), and the complete response rate (CRR) was 55.8% (95% CI, 44.1%-67.2%). Median duration of response (DOR) was not reached (NR; 95% CI, 25.59-NR).

ORR was the primary efficacy outcome measured and was defined as the percentage of patients with the best overall response (BOR) of complete response (CR) or partial response (PR) per independent review committee.

Liso-cel is recommended at a dose of 90 to 110 x 10⁶ CAR-positive T cells with a 1:1 ratio of CD4 and CD8 components.

Safety of Liso-Cel in MZL

Bristol Myers Squibb, the developer of liso-cel, shared in a news release in February that TRANSCEND FL-MZL had met its primary end point of ORR in its MZL cohort as well as its secondary end point of CRR.² According to this statement, liso-cel demonstrated safety profile consistent with prior findings.

In a presentation during the 9th Annual School of Nursing Oncology, an event hosted by Physicians’ Education Resource®, LLC, Beth Faiman, PhD, MSN, APN-BC, BMTCN, AOCN, FAAN, FAPO, said that T-cell engagers often can induce cytokine release syndrome (CRS) across disease states.

“What we’re doing is taking the marker target on the cell—for example, CD20—and then CD3, like a helping hand, will bring it together and cause cell death when you’re directing these T cells. That causes a cytokine storm and a whole host of problems. […] That cytokine release syndrome and the neurotoxicity syndrome are constants, regardless of the disease state.”

Further, Lauren Sheehan, MS MSPAS, PA-C, provided guidance on the management of adverse events common to liso-cel including CRS, neurotoxicities, serious infection, prolonged cytopenias, hypogammaglobulinemia, and secondary T-cell malignancies in her Rx Road Map for the use of liso-cel in mantle cell lymphoma (MCL).

Prior to June, the FDA has a Risk Evaluation and Mitigation Strategy (REMS) protocol in place for the monitoring and mitigation of certain safety events in patients receiving liso-cel and idecabtagene vicleucel (ide-cel; Abecma).³ These guidelines were removed in June, with the FDA reducing driving restrictions for patients from 8 weeks to 2 weeks after treatment.

Liso-Cel in Other Indications

Liso-cel was approved in May 2024 for use in previously treated relapsed/refractory follicular lymphoma, based also on findings from TRANSCEND FL-MZL. Further, the CD19-directed genetically modified autologous T-cell immunotherapy was approved in May 2024 for the treatment of adult patients with relapsed or refractory MCL who have received 2 or more prior lines of therapy including a Bruton tyrosine kinase inhibitor.

It was also approved by the FDA in June 2022 for the second-line treatment of patients with relapsed or refractory large B-cell lymphoma with primary refractory or early relapse within 12 months of frontline treatment. Liso-cel received approval for the treatment of patients with certain types of large B-cell lymphoma who have not responded to, or who have relapsed after, at least 2 other types of systemic treatment.

References

1. FDA approves lisocabtagene maraleucel for relapsed or refractory marginal zone lymphoma. FDA. December 4, 2025. Accessed December 4, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lisocabtagene-maraleucel-relapsed-or-refractory-marginal-zone-lymphoma
2. Bristol Myers Squibb Announces Positive Topline Results for Breyanzi® (lisocabtagene maraleucel) in Adult Patients with Relapsed or Refractory Marginal Zone Lymphoma. News release. Bristol Myers Squibb. February 10, 2025. Accessed December 4, 2025. https://news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibb-Announces-Positive-Topline-Results-for-Breyanzi-lisocabtagene-maraleucel-in-Adult-Patients-with-Relapsed-or-Refractory-Marginal-Zone-Lymphoma/default.aspx
3. U.S. Food and Drug Administration approves streamlined patient monitoring requirements and removal of REMS programs within Bristol Myers Squibb’s cell therapy labels. News release. Bristol Myers Squibb. June 26, 2025. Accessed December 4, 2025. https://news.bms.com/news/corporate-financial/2025/U-S--Food-and-Drug-Administration-Approves-Streamlined-Patient-Monitoring-Requirements-and-Removal-of-REMS-Programs-within-Bristol-Myers-Squibbs-Cell-Therapy-Labels/default.aspx