Lisocabtagene maraleucel (Breyanzi)

Mechanism of action

From the NCI Drug Dictionary: A preparation of a defined ratio of CD4+ and CD8+ autologous T lymphocytes transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) containing an anti-CD19 single chain variable fragment (scFv) fused to the signaling domain of 4-1BB (CD137), the zeta chain of the TCR/CD3 complex (CD3-zeta), and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, lisocabtagene maraleucel is directed to and induce selective toxicity in CD19-expressing tumor cells.

Toxicity management

• Link to REMS program

Diseases for which it is established

• Diffuse large B-cell lymphoma
• High-grade B-cell lymphoma
• Primary mediastinal B-cell lymphoma
• Transformed lymphoma

Diseases for which it is used

• Chronic lymphocytic leukemia
• Follicular lymphoma

History of changes in FDA indication

• 2024-05-15: Granted accelerated approval for adults with relapsed or refractory follicular lymphoma (FL) who have received two or more prior lines of systemic therapy. (Based on TRANSCEND-FL)
• 2021-02-05: Approved for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma after two or more lines of systemic therapy, 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. (Based on TRANSCEND NHL-001)
• 2022-06-24: Approved for adult patients with large B-cell lymphoma (LBCL) who have refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy. (Based on TRANSFORM)
• 2022-06-24: Approved for adult patients with large B-cell lymphoma (LBCL) who have 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. (Based on TRANSFORM)

History of changes in EMA indication

• 2022-04-04: Breyanzi is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL) and follicular lymphoma grade 3B (FL3B), after two or more lines of systemic therapy.
• 2023-05-25: Revised indication for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL) and follicular lymphoma grade 3B (FL3B), who relapsed within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy.

History of changes in Health Canada indication

• 2022-05-06: Initial notice of compliance

History of changes in PMDA indication

• 2021-03-22: Initial approval

Patient Drug Information

• Lisocabtagene maraleucel (Breyanzi) Package Insert

Also known as

• Code name: JCAR-017
• Generic name: liso-cel
• Brand name: Breyanzi