Topline Findings
- Regulatory Momentum: The FDA has accepted a supplemental Biologics License Application for Breyanzi in relapsed or refractory marginal zone lymphoma and granted it Priority Review, with a Prescription Drug User Fee Act action date of December 5, 2025.
- Durable Efficacy: Breyanzi showed high overall response rates and complete response rates with strong durability across key endpoints, including progression-free survival and overall survival at two years.
- Manageable Safety Profile: Consistent with prior findings, Breyanzi’s safety data showed mostly low-grade cytokine release syndrome and neurologic events, with no new safety signals observed.
The FDA has granted Priority Review status to Bristol Myers Squibb’s (BMS) supplemental Biologics License Application (sBLA) for Breyanzi (lisocabtagene maraleucel) in the treatment of adults with relapsed or refractory marginal zone lymphoma (MZL) after two or more prior systemic therapies. The sBLA was based on data from the primary analysis of the MZL cohort of the Phase II TRANSCEND FL trial (NCT04245839), which demonstrated strong and lasting responses.1,3
The application was assigned a Prescription Drug User Fee Act target action date of December 5, 2025.1
Can Breyanzi Become a New Standard for Relapsed Marginal Zone Lymphoma?
“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, VP, senior global program lead, hematology and cell therapy, BMS, 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.”
TRANSCEND FL Trial Design and Endpoints
- The open-label, global, multicenter, single-arm TRANSCEND FL trial evaluated the efficacy and safety of Breyanzi in approximately 276 patients with MZL.
- The study is structured into three phases: a pretreatment period involving screening, cell collection, and evaluation; a treatment phase beginning with lymphodepleting chemotherapy and Breyanzi infusion followed by short-term monitoring; and a posttreatment phase focused on long-term safety and disease status follow-up over five years.
- The primary endpoint of the trial was overall response rate (ORR).
- Key secondary endpoints included complete response (CR) rate, duration of response (DOR), and progression-free survival (PFS).1,2
- A total of 66 patients were deemed efficacy evaluable.
TRANSCEND FL Trial Efficacy and Safety Results
- Results showed that efficacy evaluable patients demonstrated a 95.5% ORR and a CR of 62.1%.
- At a median follow-up between 22 and 24.5 months, DOR was 88.6%, while PFS was 85.7%, and OS was 90.4%.
- No new safety signals were identified.
- Any grade cytokine release syndrome (CRS) occurred in 76% of patients, while any-grade neurologic events occurred in 33% of patients.
- Common adverse events associated with Breyanzi include fever, CRS, fatigue, musculoskeletal pain, nausea, encephalopathy, edema, and diarrhea.
- The most common grade 3 or 4 laboratory abnormalities across indications include decreases in neutrophil count, lymphocyte count, white blood cell count, platelet count, and hemoglobin.3
Disease Background and Regulatory Status
According to the Lymphoma Research Foundation, MZL accounts for approximately 8% of all cases of non-Hodgkin lymphoma. The typical age at diagnosis is around 60 years, with the condition occurring somewhat more frequently in women than in men.4
“MZL is an indolent disease but remains an area of high unmet need for patients who are relapsing and reaching later lines of treatment,” said Ricafort, in a June press release. “We are proud to present for the first time the primary analysis data from the MZL cohort of TRANSCEND FL, underscoring our commitment to unlock the full potential of cell therapy to help patients living with relapsed or refractory lymphomas. As highlighted by the data at ICML, Breyanzi continues to cover the broadest patient eligibility of any CAR T for B-cell malignancies and demonstrates a safety profile consistent with clinical trials and in the real-world setting for approved indications.”3
References
- 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). BMS. 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
- 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. Accessed August 5, 2025. https://clinicaltrials.gov/study/NCT04245839?term=(NCT04245839)&rank=1
- 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). BMS. June 16, 2025. Accessed August 5, 2025. https://news.bms.com/news/details/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?utm_source=chatgpt.com
- About Marginal Zone Lymphoma. Lymphoma Research Foundation. Accessed August 5, 2025. https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/mzl/?utm_term=&utm_campaign=DSA+-+DD&utm_source=adwords&utm_medium=ppc&hsa_acc=4581662861&hsa_cam=21426060620&hsa_grp=167915571750&hsa_ad=715010662720&hsa_src=g&hsa_tgt=dsa-437115340933&hsa_kw=&hsa_mt=&hsa_net=adwords&hsa_ver=3&gad_source=1&gad_campaignid=21426060620&gbraid=0AAAAADwLU7ycTEhCy1rKGuH4adb_aJrHz&gclid=Cj0KCQjw18bEBhCBARIsAKuAFEa-nq2XJFj2g9zyrQOLkRgOl-RPI0m7ymchbY20icQdapX80oAuoLcaAv5FEALw_wcB
