FDA Grants Accelerated Approval to CAR-T Cell Therapy for Relapsed or Refractory Follicular Lymphoma

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On March 15, 2024, Bristol Myers Squibb (BMS) announced FDA’s accelerated approval of Breyanzi (lisocabtagene maraleucel; liso-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, to treat adult patients with relapsed or refractory follicular lymphoma (FL) who have previously received two or more lines of systemic therapy (1). This accelerated approval indication was based on response rate and duration of response. Continued approval of the indication may be reliant on the positive results of confirmatory trials. Breyanzi was also added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for B-cell Lymphomas as a Category 2A recommendation for third-line and subsequent therapy for relapsed or refractory FL.

According to BMS, Breyanzi is a CD12-directed genetically modified autologous T-cell immunotherapy indication 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.”

FL has historically been considered incurable, and patients often relapse after front-line therapy, with prognosis worsening after each relapse. While there have been advances in treatment, there is still an unmet need for more options with treatment-free intervals with long-lasting, complete responses. Breyanzi is made from the patient’s own T cells, which are genetically reengineered into CAR-T cells and then delivered through infusion as a one-time treatment. It also has a 4-1BB costimulatory domain, which magnifies the growth and durability of the CAR-T cells.

BMS’ Phase II TRANSCEND FL study, which evaluated a large set of patients with relapsed or refractory FL, showed an overall response rate of 95.7% to Breyanzi. Breyanzi has received approvals in the European Union (EU), Japan, and Switzerland for second-line treatment of relapsed or refractory LBCL, and in the EU, Japan, Switzerland, the United Kingdom, and Canada for relapsed and refractory LBCL after two or more lines of systemic therapy.

“In the treatment of relapsed or refractory follicular lymphoma, patients often cycle through treatments with typically shorter responses with each new line of therapy. Those who have experienced early disease progression have notably poor prognosis,” said M. Lia Palomba, M.D., TRANSCEND investigator and lymphoma and cell therapy specialist, Memorial Sloan Kettering Cancer Center, in a BMS press release (1). “The FDA approval of liso-cel for patients with relapsed or refractory FL is an important advancement in addressing an ongoing unmet need in the FL treatment paradigm, providing patients a new option that has shown remarkably high response rates and an established safety profile.”

“The lymphoma community has felt an urgent need for advancements in the treatment of relapsed or refractory follicular lymphoma,” added Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation. “The approval of Breyanzi offers patients a new and meaningful treatment option that provides hope for lasting remission, and we are grateful to those who have contributed to this exciting milestone for patients.”

Reference

1. Bristol Myers Squibb. Bristol Myers Squibb’s CAR T Cell Therapy Breyanzi Approved by the U.S. Food and Drug Administration for Relapsed or Refractory Follicular Lymphoma. Press Release, March 15, 2024.