Instructions for Lisocabtagene maraleucel

1. Name: Lisocabtagene maraleucel、BREYANZI

2. Indications:

LisocabtageneLisocabtagene maraleucel) is a CD19-directed genetically modified autologous T-cell immunotherapy indicated for the treatment of adult patients with large B-cell lymphoma (LBCL), including unspecified diffuse large B-cell lymphoma DLBCL (includes DLBCL arising from indolent lymphomas), high-gradeB-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B in patients with:

1. Refractory disease to first-line chemoimmunotherapy or first-line chemoimmunotherapyRelapse within 12 months; or

2. Refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy, and not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or

3. Relapse or refractory disease after two or more systemic treatments.

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

3. Usage and dosage:

Lisocabutanol is for autologous use only and is for intravenous use only.

1. Dosage: For the actual number and volume of cells to be infused, please refer to the infusion release certificate (RFI certificate) of each component. Before initiating lymphodepleting chemotherapy, confirm the availability of lisocabeta root.

(1) Relapse or refractory after first-line therapyLargeB-cell lymphoma (LBCL): A single dose of lisocabeta root contains90-110×106 CAR-positive viable T cells (composed of 1:1 of CD8 and CD4 components CAR-positive live T cells), each component is packaged in 1-4 single-dose vials.

(2) Relapsed or refractory after two or more courses of treatmentLargeB-cell lymphoma: Single-dose lisocabeta root contains50-110

2. Management:

(1) Pretreatment: Before the infusion of lisocabeta root, a lymphodepleting chemotherapy regimen was given: fludarabine (fludarabine) 30mg/m2/day intravenously (IV), cyclophosphamide (cyclophosphamide) 300mg/m2/day intravenously, for a total of 3 days. Lisocabuta root is infused 2-7 days after completion of lymphadenectomy chemotherapy.

(2) Premedication: To minimize the risk of infusion reactions, premedicate patients with acetaminophen (650 mg orally) and diphenhydramine (25-50 mg intravenously or orally) or another H1 antihistamine 30-60 minutes before treatment with lisocabeta root. Avoid prophylactic use of systemic corticosteroids as they may interfere with the activity oflisocabeta root.

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

4. Adverse reactions:

In clinical studies of lisocabetagen, the most common side effects include neutropenia, anemia or thrombocytopenia, and cytokine release syndrome (a potentially life-threatening condition that may cause fever, vomiting, shortness of breath, pain, and hypotension).

5. Storage:

Lisocabeta root consists of genetically modified autologousT cells and is supplied in vials as separate frozen suspensions of each CD8 component and CD4 component in the vapor phase of a liquid nitrogen transporter directly to the cell laboratory or clinical pharmacy associated with the infusion center. The vials are stored in the vapor phase of liquid nitrogen in a temperature-monitored system (below or equal to minus 130°C) after patient information is received and clarified. Thaw lisocabetagen before infusion.

6. Mechanism of action:

Lisocabetagen is a CD19-directed genetically modified autologous cellular immunotherapy administered as a defined composition to reduce variability in CD8-positive and CD4-positive T cell doses. The CAR consists of a single-chain variable fragment (scFv) derived from an FMC63 monoclonal antibody, an IgG4 hinge region, a CD28 transmembrane domain, a 4-1BB (CD137) costimulatory domain, and a CD3 activation domain. CD3 signaling is critical for initiating activation and anti-tumor activity, while 4-1BB (CD137) signaling enhances the expansion and persistence of lisocabeta root. CAR binds to CD19 expressed on the cell surface of tumor and normal B cells, inducing the activation and proliferation of CAR T cells, the release of pro-inflammatory cytokines, and the cytotoxic killing of target cells.xa0