Chinese introduction to the instructions for Lisocabtagene maraleucel

1. Common name:Lisocabtagene maraleucel

Product name:BREYANZI

Other names: Lisso Cabbage Root, Lisso Cabernet Sauvignon

2. Indications:

Lisocabtagene (Lisocabtagene maraleucel) is indicated for the treatment of the following conditions:

1. LargeB-cell lymphoma (LBCL; non-Hodgkin lymphoma): Indicated for the treatment of adult patients with largeB-cell lymphoma (LBCL), including diffuse large B-cell malignant lymphoma (DLBCL) not otherwise specified (including DLBCL due to indolent lymphoma, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma) who have:

•Refractory disease is switched to first-line chemotherapy or relapses within 12 months after first-line chemotherapy; or

•For disease refractory to first-line chemotherapy or relapsed after first-line chemotherapy, ineligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or

•Relapsed or refractory disease after 2 or more lines of systemic therapy.

Restrictions on Use:BREYANZI is not indicated for the treatment of patients with primary central nervous system (CNS) lymphoma.

2. Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL): Applicable to the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received at least 2 treatments, including Bruton's tyrosine kinase (BTK) inhibitors and B-cell lymphoma 2 (BCL-2) inhibitors.

3. Follicular lymphoma (FL): Applicable to the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received two or more lines of systemic therapy.

4. Mantle cell lymphoma (MCL): Applicable to the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have previously received at least 2 systemic therapies, including Bruton's tyrosine kinase (BTK) inhibitors.

5. Marginal zone lymphoma (MZL): Suitable for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least 2 systemic treatments.

3. Usage and dosage:

Lisocabeta root is for autologous use only and is for intravenous use only. For the actual number and volume of cells infused, please refer to the infusion release certificate (RFI certificate) for each component. Before initiating lymphodepleting chemotherapy, confirm the availability of lisocabeta root.

1) ForLBCL patients:

•After first-line therapy, dose is 90 to 110x106 CAR-positive live T cells (composed of 1:1 CAR-positive live T cells of CD8 and CD4 components) in 1-4 single-dose vials for each component.

•After second or multiple lines of treatment, the dose is 50-110x10* CAR-positive viable T cells.

2) For CLL/SLL, FL, MCL and MZL patients: Dosage is 90 to 110x10 CAR-positive live T cells (consisting of 1:1 CAR-positive live T cells of CD8 and CD4 components), each in 1-4 single-dose vials.

3) If the patient has unresolved serious adverse events, active uncontrolled infection, or active graft-versus-host disease (GVHD) from prior chemotherapy, delay the infusion of lisocabetagen.

4. Adverse reactions:

In clinical studies of lisocabeta root, side effects included allergic reactions, serious infections, low blood cell counts and weakened immune systems, a decrease in neutrophils (a type of white blood cell that fights infections), red blood cells, or platelets (components that help blood clot), as well as cytokine release syndrome (a potentially life-threatening condition that can cause fever, vomiting, shortness of breath, pain, and hypotension), headache, musculoskeletal pain, fatigue, constipation, and fever.

5. Supply and storage:

Breyanzi consists of genetically modified autologous T cells and is supplied in single-dose vials with each CD8 component and CD4 component separately frozen and suspended. Each CD8 or CD4 component is packaged in a carton containing up to 4 vials, depending on the concentration of cryopreserved drug product CAR-positive viable T cells. Each CD8 component and CD4 component carton is in an outer carton. Brevanzi is delivered in the vapor phase in a liquid hydrogen carrier directly to the cell laboratory or clinical pharmacy associated with the infusion center. .Infusion release certificate confirming patient identity upon receipt. Store vials in the vapor phase of liquid nitrogen in a temperature-monitored system (below or equal to minus 130°C). Thaw Breyanzi before infusion.

6. Mechanism of action:

Lisocabetagen is a chimeric antigen receptor (CAR) T cell therapy targetingCD19 (also known as B lymphocyte surface antigen B4.10). The CAR consists of the FMC63 monoclonal antibody single-chain variable fragment, IgG4 hinge region, CD28 transmembrane domain, 4-1BB costimulatory domain, and CD3ζ activation domain. 10 FMC63 is an IgG2a mouse monoclonal antibody targeting CD19. The IgG4 hinge region can interact with Fcγ receptors to modulate hematopoietic cell responses. The CD28 transmembrane domain can stimulate T cell activity or tolerance. 4-1BB enhances the activity of cytotoxic T cells and the production of interferon-γ. The CD23ζ cytoplasmic domain mediates T cell activation through CD2, a T cell surface adhesion molecule.

Reference materials:https://www.breyanzi.com/