EMA Validates Bristol Myers Squibb’s CAR T Therapy Breyanzi for Relapsed/Refractory Follicular Lymphoma

Bristol Myers Squibb has announced that the European Medicines Agency (EMA) has validated its application to expand the use of Breyanzi® (lisocabtagene maraleucel; liso-cel) for treating adult patients with relapsed or refractory follicular lymphoma (FL) who have undergone two or more prior lines of systemic therapy. This validation implies that the submission is complete and allows the EMA's scientific review to begin.

Follicular lymphoma (FL) is a common form of non-Hodgkin lymphoma (NHL), constituting 20 to 30 percent of all NHL cases. Despite being historically considered incurable, advancements like Breyanzi represent hope for more durable and complete responses. Patients with relapsed or refractory FL tend to have shorter responses to each new therapy.

Anne Kerber, Senior Vice President of Late Clinical Development in Hematology, Oncology, and Cell Therapy at Bristol Myers Squibb, highlighted the significance of this development. She emphasized that Breyanzi stands out as a differentiated CAR T cell therapy and expressed anticipation to collaborate with the EMA to bring this treatment to FL patients, aiming at improving outcomes and extending remission periods.

The application builds on data from the Phase 2 TRANSCEND FL study, the largest clinical trial to date examining a CAR T cell therapy in people with relapsed or refractory indolent NHL, including FL. The study involved adults with FL who had received Breyanzi as a second-line or third-line therapy. Results have shown that Breyanzi achieves a high overall response rate, and the responses are both deep and durable. The safety profile observed in the study aligns with the known and manageable safety profile of Breyanzi from other clinical trials.

Breyanzi is already approved in the European Union for treating adult patients with various forms of relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), and FL grade 3B (FL3B). It is also approved for patients who relapse within 12 months of completing first-line chemoimmunotherapy or are refractory to it, and for those who have undergone two or more lines of systemic therapy.

Additionally, Japan’s Ministry of Health, Labour and Welfare has approved a supplemental New Drug Application for Breyanzi for treating relapsed or refractory follicular lymphoma after one prior line of systemic therapy in patients with high-risk FL, and after two or more lines of systemic therapy. This makes Breyanzi the first CAR T approved in the second-line setting globally and marks its third approval in Japan.

Breyanzi functions as a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. It is created from the patient’s own T cells, which are collected and genetically modified to become CAR T cells, and then infused back into the patient as a one-time treatment.

Breyanzi is approved in the U.S. for treating relapsed or refractory large B-cell lymphoma (LBCL) after at least one prior therapy line, and has received accelerated approval for relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma after at least two prior therapies, and for relapsed or refractory follicular lymphoma in the third-line plus setting. It is also approved in Switzerland and the European Union for the second-line treatment of relapsed or refractory LBCL, and in Canada, the UK, and Japan for relapsed and refractory LBCL after two or more lines of systemic therapy, among other indications.

The clinical development program for Breyanzi by Bristol Myers Squibb includes ongoing studies in different types of lymphoma.