Key Takeaways
- Breyanzi Achieves High Overall Response Rate in R/R MZL. In the Phase II TRANSCEND FL trial, Breyanzi demonstrated a 95.5% overall response rate and a 62.1% complete response rate in patients with relapsed or refractory marginal zone lymphoma (MZL).
- Durable Efficacy Observed in Long-Term Follow-Up. At median follow-ups nearing two years, Breyanzi showed an 88.6% duration of response, 85.7% progression-free survival, and 90.4% overall survival in the MZL cohort.
- Favorable Safety Profile with No New Safety Signals. Breyanzi maintained a consistent safety profile with no grade 4/5 cytokine release syndrome or neurologic events reported in treated patients with R/R marginal zone lymphoma.
Findings from the primary analysis of the marginal zone lymphoma (MZL) cohort of the Phase II TRANSCEND FL (NCT04245839) trial showed significant and durable efficacy for Breyanzi(lisocabtagene maraleucel; Bristol Myers Squibb) treating patients with relapsed or refractory (R/R) disease.1,2 According to Bristol Myers Squibb, this is the largest clinical trial to date evaluating a chimeric antigen receptor (CAR) T-cell therapy in patients with R/R indolent B cell NHL, including high-risk second-line FL.
Phase II TRANSCEND FL Trial Highlights Breyanzi’s Potential in Indolent B-cell NHL
These data expand on positive topline findings from the trial reported earlier this year and will be presented this week at the 2025 International Conference on Malignant Lymphoma.
“[MZL] is a slow-growing cancer that, for many, has a favorable prognosis. But for those patients who relapse or become refractory, the disease can be quite aggressive, and there is a need for new effective and tolerable treatment options to address this unmet critical need,” Rosanna Ricafort, vice president and head of Late Development Program Leadership, Hematology and Cell Therapy, Bristol Myers Squibb, said in a press release. “We are pleased that the TRANSCEND FL study supports the potential of Breyanzi in [MZL] and look forward to presenting detailed results from the study at an upcoming medical meeting.”1
Breyanzi’s Expanding Role in Hematologic Malignancies
Breyanzi is a CD19-directed CAR T-cell therapy that is made from a patient’s own T cells. The cells are taken from a patient and genetically reengineered to become CAR T cells, which are subsequently infused back into the patient via a one-time infusion.
Breyanzi has been approved by the FDA to treat:
- Adults with large B-cell lymphoma (LBCL), including diffuse LBCL not otherwise specified, high-grade B cell lymphoma, primary mediastinal LBCL, and follicular lymphoma (FL) grade 3B, including:
- Patients with refractory disease to first-line chemoimmunotherapy or who relapse within 12 months of first-line chemoimmunotherapy.
- Patients with refractory disease to first-line chemoimmunotherapy or relapse following first-line chemoimmunotherapy and who ineligible for hematopoietic stem cell transplantation because of comorbidities or age.
- Patients with R/R disease following two or more lines of systemic therapy.
- Breyanzi was approved in May 2024 for adults with R/R mantle cell lymphoma who were previously administered at least two lines of systemic therapy that included a Bruton tyrosine kinase (BTK) inhibitor.3
- Breyanzi was granted an accelerated approval in May 2024 for adults with R/R follicular lymphoma who previously received two or more lines of systemic therapy.4
- Breyanzi was also granted an accelerated approval in March 2024 for adults with R/R chronic lymphocytic leukemia or small lymphocytic lymphoma who were previously administered at least two lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.5
“With Breyanzi, we are delivering on the promise of cell therapy by offering a definitive treatment option for some of the most difficult-to-treat lymphomas,” Bryan Campbell, senior vice president, head of Commercial, Cell Therapy, Bristol Myers Squibb, said in a prior press release. “We are proud of the advances we are making to bring our differentiated CAR T-cell therapy to the most patients across indications and lines of therapy to ensure treatment options that provide improved outcomes are available when most needed.”3
TRANSCEND FL Trial Design and Endpoints
- The open-label, global, multicenter, single-arm TRANSCEND FL trial evaluated the efficacy and safety of Breyanzi in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (NHL), including FL and MZL.
- The trial’s primary endpoint is overall response rate (ORR), with secondary endpoints that include complete response (CR) rate, duration of response (DOR), and progression-free survival (PFS).
Breyanzi Produces High Response Rates and Lasting Remissions in R/R MZL
The MZL cohort of the trial included adults with R/R disease administered Breyanzi in the third-line plus setting at a target dose of 100 x 106 CAR-positive viable T cells.
- Among 66 efficacy-evaluable patients with R/R MZL administered Breyanzi, the drug produced an ORR of 95.5% (95% CI: 87.3-99.1; one-sided p<0.0001).
- Among these patients, 62.1% achieved a CR (95% CI: 49.3-73.8; one-sided p<0.0001) as determined by an independent review committee.
- At a median follow-up of 21.6 months, DOR was 88.6% among patients administered Breyanzi.
- At a median follow-up of 23.8 months, PFS was 85.7% among patients administered Breyanzi.
- At a median follow-up of 24.5 months, overall survival was 90.4% among patients administered Breyanzi.
Favorable Safety Profile Observed in Marginal Zone Lymphoma Patients
In terms of safety, the profile of Breyanzi was consistent prior findings and no new safety signals were reported.
- Any grade cytokine release syndrome (CRS) was reported in 76% of patients administered Breyanzi, with grade 3 CRS reported in 4% of patients with no grade 4/5 CRS.
- Any grade neurologic events (NEs) occurred in 33% of patients administered Breyanzi, with grade 3 NEs reported in 4% of patients and no grade 4/5 NEs.
Investigators will continue to track ORR and safety through the trial’s final analysis.
References
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). News release. Bristol Myers Squibb. June 16, 2025. Accessed June 16, 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
2. 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 May 23, 2025. Accessed June 16, 2025. https://clinicaltrials.gov/study/NCT04245839
3. 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. Bristol Myers Squibb. May 30, 2024. Accessed June 16, 2025. https://news.bms.com/news/details/2024/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-Breyanzi-as-a-New-CAR-T-Cell-Therapy-for-Relapsed-or-Refractory-Mantle-Cell-Lymphoma/default.aspx
4. Bristol Myers Squibb’s CAR T Cell Therapy Breyanzi Approved by the U.S. Food and Drug Administration for Relapsed or Refractory Follicular Lymphoma. News release. Bristol Myers Squibb. May 15, 2024. Accessed June 16, 2025. https://news.bms.com/news/details/2024/Bristol-Myers-Squibbs-CAR-T-Cell-Therapy-Breyanzi-Approved-by-the-U.S.-Food-and-Drug-Administration-for-Relapsed-or-Refractory-Follicular-Lymphoma/default.aspx
5. US FDA approves Bristol Myers Squibb’s Breyanzi ® as the first and only CAR T cell therapy for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). News release. Bristol Myers Squibb. March 14, 2024. Accessed June 16, 2025. https://news.bms.com/news/details/2024/U.S.-FDA-Approves-Bristol-Myers-Squibbs-Breyanzi--as-the-First-and-Only-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Chronic-Lymphocytic-Leukemia-CLL-or-Small-Lymphocytic-Lymphoma-SLL/default.aspx
