Bristol Myers Squibb (NYSE: BMY) has announced positive topline results from the Phase 2 TRANSCEND FL trial, evaluating Breyanzi® (lisocabtagene maraleucel) in adult patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma. The study met its primary endpoint in the marginal zone lymphoma (MZL) cohort, showing a statistically significant and clinically meaningful overall response rate (ORR) in these patients.
The Phase 2 TRANSCEND FL study also successfully met its key secondary endpoint of complete response rate (CRR). In this topline analysis, Breyanzi continued to exhibit durable responses and a consistent safety profile, with no new safety signals observed. This marks the fifth type of cancer in which Breyanzi has demonstrated clinically meaningful benefits, reinforcing its position as the broadest CD19-directed CAR T cell therapy available for B-cell malignancies.
Addressing an Unmet Need in Marginal Zone Lymphoma
“Marginal zone lymphoma is a slow-growing cancer that, in many cases, has a favorable prognosis,” stated Rosanna Ricafort, Vice President, Head of Late Development Program Leadership, Hematology, and Cell Therapy at Bristol Myers Squibb. “However, for patients who relapse or develop refractory disease, the condition can become aggressive. There is a clear need for effective and well-tolerated treatment options. We are encouraged that the TRANSCEND FL study supports Breyanzi’s potential in treating marginal zone lymphoma and look forward to sharing the detailed results at an upcoming medical meeting.”
Bristol Myers Squibb acknowledges the invaluable contribution of the patients and investigators involved in the TRANSCEND FL clinical trial.
About the TRANSCEND FL Study
TRANSCEND FL (NCT04245839) is an open-label, global, multicenter, Phase 2, single-arm study designed to evaluate the efficacy and safety of Breyanzi in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma, including follicular lymphoma and marginal zone lymphoma. The primary outcome measure is overall response rate (ORR), while secondary outcome measures include complete response rate (CRR), duration of response (DOR), and progression-free survival (PFS).
Understanding Marginal Zone Lymphoma
Marginal zone lymphoma (MZL) is the second most common form of slow-growing non-Hodgkin lymphoma (NHL), representing about 7% of all NHL cases. The median age of diagnosis is 67 years. MZL occurs when white blood cells form clusters in lymph nodes or other organs. The disease is classified into three main subtypes:
- Extranodal MZL (60%): Affects organs such as the gastrointestinal tract, skin, and lungs.
- Nodal MZL (30%): Involves the lymph nodes.
- Splenic MZL (10%): Involves the spleen.
While initial treatments often lead to long remission periods, relapses are common, sometimes occurring multiple times over several years. A small percentage of MZL cases transform into diffuse large B-cell lymphoma, a more aggressive form of NHL.
About Breyanzi
Breyanzi is a CD19-directed CAR T cell therapy incorporating a 4-1BB costimulatory domain to enhance CAR T cell expansion and persistence. It is an autologous therapy, meaning it is derived from a patient’s own T cells. These cells are collected, genetically engineered to express a CAR protein targeting CD19, and then infused back into the patient as a one-time treatment.
Breyanzi is currently approved in the U.S. for the treatment of:
- Relapsed or refractory large B-cell lymphoma (LBCL) after at least one prior line of therapy.
- Relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior lines of therapy.
- Relapsed or refractory follicular lymphoma (FL) after two or more prior lines of systemic therapy.
- Relapsed or refractory mantle cell lymphoma (MCL) in patients who have received at least two prior lines of systemic therapy, including a BTK inhibitor.
Additionally, Breyanzi is approved in Japan and Europe for second-line treatment of relapsed or refractory LBCL and in multiple countries for relapsed and refractory LBCL after two or more prior lines of systemic therapy. It has also been approved in Japan for relapsed or refractory high-risk follicular lymphoma after one prior line of systemic therapy.
U.S. FDA-Approved Indications and Important Safety Information
Breyanzi is indicated for the treatment of adult patients with:
- Large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have relapsed or refractory disease.
- Relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
- Relapsed or refractory follicular lymphoma (FL) after two or more prior lines of systemic therapy.
- Relapsed or refractory mantle cell lymphoma (MCL) after at least two prior lines of systemic therapy, including a BTK inhibitor.
Breyanzi carries a Boxed Warning for Cytokine Release Syndrome (CRS) and neurologic toxicities, including fatal and life-threatening reactions.
Cytokine Release Syndrome (CRS)
- Occurred in 54% of patients in clinical trials, with Grade ≥3 CRS occurring in 3.2% of patients.
- Symptoms include fever, hypotension, tachycardia, chills, hypoxia, and headache.
- Severe cases require treatment with tocilizumab and corticosteroids.
Neurologic Toxicities
- Observed in 31% of patients, with Grade ≥3 cases in 10% of patients.
- Symptoms include encephalopathy, tremor, aphasia, headache, dizziness, and delirium.
- Can occur concurrently with or independently of CRS.
Other Safety Considerations:
- Serious infections and febrile neutropenia may occur.
- Prolonged cytopenias have been reported.
- Hypogammaglobulinemia and B-cell aplasia may lead to increased risk of infections.
- Patients must be monitored for secondary malignancies, including T-cell malignancies.
Breyanzi is available only through the BREYANZI REMS program, Bristol which ensures that healthcare facilities meet the necessary safety requirements for treatment Bristol administration.
Bristol Myers Squibb: Advancing Cell Therapy
Bristol Myers Squibb continues to pioneer cell therapy for blood cancers and aims Bristol to expand into new therapeutic areas,Bristol including autoimmune diseases. As the only company with two distinct CAR T cell therapies approved globally, BMS remains at the forefront Bristol of cell therapy innovation.
For further details about Breyanzi and ongoing clinical trials, visit clinicaltrials.gov.
