Bristol Myers Squibb announced that the European Commission (EC) has granted approval to Breyanzi (lisocabtagene maraleucel; liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.
“This additional approval for Breyanzi in FL represents a critical step forward in our mission to deliver on the transformational promise of cell therapy for more patients across Europe,” said Emma Charles, senior vice president, Europe Region, Bristol Myers Squibb. “While significant advancements have been made in the last two decades, there still remains unmet need for patients. Newer treatments for FL, like Breyanzi, have shown impactful results in clinical trials, with the opportunity to deliver lasting results in the routine care setting.”
The decision is based on results from the global, phase 2 TRANSCEND FL study, the largest clinical trial to date to evaluate a CAR T cell therapy in patients with relapsed or refractory indolent non-Hodgkin lymphoma (NHL), including FL. Among patients treated in the third-line plus setting, Breyanzi demonstrated a high overall response rate of 97.1% (95% CI: 91.7–99.4) and complete response (CR) rate of 94.2% (95% CI: 87.8–97.8), the study’s primary and key secondary endpoints, respectively. Responses were rapid, durable and demonstrated sustained efficacy, with a median time to first response of 0.95 months (range: 0.6 to 3.3 months) and 75.7% (95% CI: 66.0–83.0) of patients still in response at 18 months.
Safety results were consistent with the well-established safety profile of Breyanzi observed across clinical trials and approved indications, with no new safety signals observed in FL. In all patients treated in the TRANSCEND FL study (second-line plus), any grade cytokine release syndrome (CRS) occurred in 58% of patients, with only 0.8% of patients experiencing Grade 3 CRS. The median time to onset was 6 days (range: 1 to 17 days). Any grade neurologic toxicities occurred in 16% of patients, including Grade 3 in 3% of patients. The median time to onset of the first event was 8 days (range: 4 to 16 days).
This expanded approval is applicable to all European Union (EU) member states as well as the European Economic Area (EEA) countries Iceland, Norway and Liechtenstein. Breyanzi is also approved in the EU for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL) and FL grade 3B (FL3B), who relapsed within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy, and for the treatment of adult patients with relapsed or refractory DLBCL, PMBCL, and FL3B after two or more lines of systemic therapy.
TRANSCEND FL (NCT04245839) is an open-label, global, multicenter, phase 2, single-arm study to determine the efficacy and safety of Breyanzi in adult patients with relapsed or refractory indolent B-cell NHL, including FL. The primary outcome measure is overall response rate, including best overall response of complete response or partial response as determined by an Independent Review Committee. Secondary outcome measures include complete response rate, duration of response, progression-free survival and safety.
Follicular lymphoma (FL) is the second most common form of NHL, accounting for 20-30% of all NHL cases. FL develops when white blood cells cluster together to form lumps in a person’s lymph nodes or organs. FL is an incurable disease, with patients frequently relapsing following front-line therapy and prognosis worsening after each subsequent relapse. Despite advances in treatment, there remains an unmet need for additional options for relapsed or refractory FL that offer treatment-free intervals with durable, complete responses.
Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. Breyanzi is made from a patient’s own T cells, which are collected and genetically reengineered to become CAR T cells that are then delivered via infusion as a one-time treatment.
Breyanzi is approved in the US for the treatment of relapsed or refractory large B-cell lymphoma (LBCL) after at least one prior line of therapy, has received accelerated approval for the treatment of relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma after at least two prior lines of therapy and relapsed or refractory FL in the third-line plus setting, and is approved for the treatment of relapsed or refractory mantle cell lymphoma in the third-line plus setting. Breyanzi is also approved in Japan, the EU, Switzerland, the UK and Canada for the treatment of relapsed or refractory LBCL after at least one prior line of therapy; and in Japan for the treatment of patients with relapsed or refractory high-risk FL after one prior line of systemic therapy and in patients with relapsed or refractory FL after two or more lines of systemic therapy.
Bristol Myers Squibb’s clinical development programme for Breyanzi includes clinical studies in other types of lymphoma.
Breyanzi is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:
adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:
refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or
relapsed or refractory disease after two or more lines of systemic therapy.
Limitations of use:
Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.
adult patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
adult patients with relapsed or refractory follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor.
A pioneer in harnessing the immune system to fight cancer and an established leader in cell therapy, Bristol Myers Squibb is uniquely positioned to unlock the full potential of this technology across blood cancers and within new frontiers, including autoimmune disease.
Bristol Myers Squibb is currently the only company with two approved CAR T cell therapies with two distinct targets, available in major markets around the world. Our bold vision for the future is one in which hundreds of thousands of patients can be treated with cell therapy’s transformational potential.
The building blocks to realize this ambition—a promising and differentiated pipeline, extensive translational and clinical data sets, a deep bench of talent, and robust manufacturing capabilities— are in our cells. We are laser-focused on advancing the field of cell therapy toward a true revolution for patients.
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.