On Monday, Bristol Myers Squibb (BMS) announced the European Medicines Agency (EMA) validated the company’s Type II variation application, expanding treatment for Breyanzi (lisocabtagene maraleucel) to include adult patients with relapsed or refractory follicular lymphoma (FL).  

To qualify, patients must have received two or more previous lines of systemic therapy. 

“Follicular lymphoma impacts a significant number of people, and those with relapsed or refractory disease tend to experience shorter responses with each new line of therapy,” said Anne Kerber, senior vice president, head of late clinical development, hematology, oncology and cell therapy (HOCT) at BMS.  

The EMA’s validation confirms that the submission is complete, enabling scientific review of the application to begin under the agency’s centralized review procedure. The application is supported by data from the Phase II TRANSCEND FL study, which concluded high complete response rates and low occurrences of cytokine release syndrome.  

BMS identified the study as 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. 

Breyanzi already has European Union (EU) approval to treat adults 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. It is also approved for adults with relapsed or refractory DLBCL, PMBCL, and FL3B after two or more lines of systemic therapy. 

A spokesperson for BMS told BioProcess Insider that the company “is investigating the use of Breyanzi in potential additional indications, including 2L FL and relapsed or refractory marginal zone lymphoma (MZL).” The spokesperson added, “Beyond our clinical development program, we are also working quickly to expand the availability of Breyanzi into new markets and across indications, including planned launches in additional countries in 2025.” 

Manufacturing and Delivering CAR T Therapies 
The spokesperson told us that “the complexity of delivering autologous CAR T cell therapies is unlike any other traditional biologic or small molecule medicine, using a patient’s own cells to start a highly sophisticated and personalized manufacturing process.” 

To receive treatment for Breyanzi and other autologous therapies, patients must travel to a licensed treatment center where their T cells are collected through apheresis, which can take several hours. BMS has activated more than 200 of these facilities globally. Patients can browse 130 US facilities through an online treatment center locator.  

After cells are collected, BMS sends them to one of its four cell-therapy facilities, located in Warren and Summit, NJ, Bothell, WA, and Devens, MA. The company is also making progress on a new facility in Leiden, Netherlands to further expand its global manufacturing network.  

“T cells that have been collected from the patient are shipped to a specialized cell therapy manufacturing facility where they undergo genetic ‘reprogramming’ to become CAR T cells,” the spokesperson said. “The CAR T cells are then multiplied to create the recommended dose for Breyanzi, consisting of millions of CAR T cells, which then undergo rigorous testing and quality control before being shipped back to the patient at a CAR T cell treatment center.”  

Patients then return to the treatment center and receive a one-time Breyanzi infusion in a process that takes about an hour. The CAR T cells then expand throughout the body and attack target cells.  

The spokesperson said BMS has designed a robust manufacturing and supply-chain platform that is capable of providing Breyanzi on a commercial scale. “We continue to proactively expand our capacity to support increased patient demand that comes with recently approved additional indications.”