FDA Approves BMS’s Liso-Cel for R/R Marginal Zone Lymphoma

The FDA has approved Bristol Myers Squibb’s autologous CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy lisocabtagene maraleucel (liso-cel, marketed as Breyanzi) for the treatment of relapsed/refractory (r/r) marginal zone lymphoma (MZL) in adults who have previously been treated with at least 2 lines of systemic therapy.¹

The agency's decision was based on results from an r/r MZL cohort in the phase 2 TRANSCEND FL clinical trial (NCT04245839), a multicenter, open-label study. The cohort included adults with r/r MZL who had previously been treated with 2 or more previous lines of systemic therapy or who had relapsed following hematopoietic stem cell transplant (HSCT) and was open to patients with an Eastern Cooperative Oncology Group performance status of 1 or lower.

Data from the r/r MZL cohort were presented earlier this year at the 2025 International Conference on Malignant Lymphoma (ICML), held June 17 to June 21 in Lugano, Switzerland.² Among the 66 efficacy evaluable patients with R/R MZL who were treated with liso-cel, the overall response rate (ORR) was 95.5% (95% CI: 87.3%-99.1%; one-sided P <.0001) and the complete response rate was 62.1% (95% CI: 49.3%-73.8%; one-sided P < .0001). The 24-month rate for duration of response was 88.6% (median follow-up, 21.6 months), the 24-month rate for progression-free survival was 85.7% (median follow-up, 23.8 months), and the 24-month rate for overall survival was 90.4% (median follow-up, 24.5 months).

According the the FDA, liso-cel has warnings and precautions in its prescribing information for "cytokine release syndrome, neurologic toxicities, hypersensitivity reactions, serious infections, prolonged cytopenias, hypogammaglobulinemia, secondary malignancies, and immune effector-cell-associated hemophagocytic lymphohistiocytosis-like syndrome."¹ The recommended dose for the product constitutes 90 to 110×10⁶ CAR-positive viable T-cells having a 1:1 ratio of CD4 and CD8 components.

“Liso-cel achieved high, lasting response rates in patients with R/R MZL, underscoring the potential of this one-time therapy to significantly improve patient outcomes,” TRANSCEND FL study investigator M. Lia Palomba, MD, a lymphoma and cell therapy specialist at Memorial Sloan Kettering Cancer Center, said in a June 2025 statement.² “Currently, the median survival for patients with marginal zone lymphoma with multiple relapses is 3 to 5 years, signifying an urgent need for transformative therapies that can effectively address this hard-to-treat disease.”

Bristol Myers Squibb's supplemental biologics license application that lead to today's decision was accepted by the FDA with priority review in August 2025.³ Liso-cel has been previously approved for indications in a number of other hematologic malignancies, including large B-cell lymphoma, chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphoma, and mantle cell lymphoma (MCL).

Notably, when liso-cel was approved for r/r MCL in May 2024, it became the CAR-T with FDA approval for the broadest range of B-cell malignancies.⁴ The r/r MZL approval specifically indicates the therapy for adults with r/r MCL who have been previously treated with at least 2 lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. Shortly after this approval, CGTLive® spoke with Michael Wang, MD, a professor in the Department of Lymphoma/Myeloma at MD Anderson Cancer Center, who served as lead investigator on the phase 1 TRANSCEND NHL 001 clinical trial (NCT02631044) that led to liso-cel's approval in r/r MCL. In the interview, Wang expressed enthusiasm regarding the approval and noted that it would provide an important new option for older and frailer patients with r/r MCL.

“It will be a very important part of our treatment paradigm," Wang told CGTLive.

REFERENCES
1. FDA approves lisocabtagene maraleucel for relapsed or refractory marginal zone lymphoma. News release. 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 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 December 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. 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 December 4, 2025. https://news.bms.com/news/corporate-financial/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
4. U.S. Food and Drug Administration Approves Bristol Myers Squibb’s Breyanzi as a New CAR T Cell Therapy for Relapsed or Refractory Mantle Cell Lymphoma. News release. FDA. May 30, 2024. Accessed May 30, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma