Breyanzi CAR-T Therapy Receives FDA Accelerated Approval for Expanded Indication in Adult Patients with Relapsed or Refractory Follicular Lymphoma (FL)
Breyanzi CAR-T Therapy Receives FDA Accelerated Approval for Expanded Indication in Adult Patients with Relapsed or Refractory Follicular Lymphoma (FL)
Expanded Indication for Breyanzi
On May 15th, 2024 (local time), the U.S. Food and Drug Administration (FDA) announced the accelerated approval of Breyanzi (lisocabtagene maraleucel), Bristol Myers Squibb’s CAR-T therapy, for an expanded indication to treat adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies. This comes after Breyanzi received accelerated approval from the FDA in March of this year for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (R/R CLL) or small lymphocytic lymphoma (SLL). This latest approval also earned Breyanzi an orphan drug designation.
This accelerated approval is based on the positive results from the Phase 2 TRANSCEND FL clinical trial. In this single-arm, open-label clinical trial, patients treated with Breyanzi achieved an overall response rate (ORR) of 95.7% (95% CI: 89.5%, 98.8%) at a median follow-up of 16.8 months, with a median duration of response (DOR) not yet reached (95% CI: 18.04, NR).
Clinical Study
The TRANSCEND-FL study (NCT04245839) provided clinical evidence for this approval. It was a Phase 2, open-label, multicenter, single-arm study that enrolled adult patients with relapsed or refractory FL who had received at least two prior systemic therapies (including an anti-CD20 antibody and an alkylating agent). The primary efficacy endpoints were the overall response rate (ORR), defined as the proportion of patients with a best overall response of complete or partial remission after Breyanzi infusion as determined by an independent review committee, and the duration of response (DOR).
Patients could receive bridging therapy to control their disease after leukapheresis and before receiving lymphodepleting chemotherapy (fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2 for 3 days) and subsequent Breyanzi administration.
The TRANSCEND-FL study results showed an ORR of 95.7% (95% CI: 89.5% – 98.8%). At a median follow-up of 16.8 months (95% CI: 16.3 – 17.0), the median DOR was not reached (95% CI: 18.04 – not reached).
Dosage and Administration
The recommended dose of Breyanzi is a flat dose of 90 × 106 – 110 × 106 CAR-positive viable T cells, with a 1:1 ratio of CD4:CD8 components.
Adverse Reactions
Common adverse reactions (≥20%) include cytokine release syndrome, headache, musculoskeletal pain, fatigue, constipation, and fever.
FL is the second most common indolent form of non-Hodgkin lymphoma (NHL), accounting for 20% to 30% of all NHL cases. Most FL patients are diagnosed at over 50 years of age. In FL, white blood cells accumulate in the lymph nodes or organs, forming tumors. FL is characterized by a pattern of remission and relapse, with treatment becoming more difficult as the disease relapses or progresses.
Breyanzi is an autologous CAR-T cell therapy targeting the CD19 antigen. It was initially approved by the FDA in February 2021 for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy. The unique aspect of this therapy is the controlled ratio of CD8-positive and CD4-positive T cells in the CAR-T product, which aims to better manage the toxicity of the cell therapy. The 4-1BB costimulatory domain in the chimeric antigen receptor enhances the expansion and persistence of the CAR-T cells.