Lisocabtagene maraleucel

BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated 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 2 or more lines of systemic therapy.

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

For autologous use only. For intravenous use only. • Do NOT use a leukodepleting filter. • Administer a lymphodepleting regimen of fludarabine and cyclophosphamide before infusion of BREYANZI. • Verify the patient’s identity prior to infusion. • Premedicate with acetaminophen and an H 1 antihistamine. • Confirm availability of tocilizumab prior to infusion. • Dosing of BREYANZI is based on the number of chimeric antigen receptor (CAR)-positive viable T cells. For LBCL: • after one line of therapy, the dose is 90 to 110 × 10 6 CAR-positive viable T cells. • after two or more lines of therapy, the dose is 50 to 110 × 10 6 CAR-positive viable T cells. For CLL/SLL, FL, MCL and MZL: • the dose is 90 to 110 × 10 6 CAR-positive viable T cells.

None. None.

Boxed warning (cytokine release syndrome, neurologic toxicities, and secondary hematological malignancies •): Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving BREYANZI. Do not administer BREYANZI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids. • Hypersensitivity Reactions: Monitor for hypersensitivity reactions during infusion. • Serious Infections: Monitor patients for signs and symptoms of infection, treat appropriately. • Prolonged Cytopenias: Patients may exhibit Grade 3 or higher cytopenias for several weeks following BREYANZI infusion. Monitor complete blood counts. • Hypogammaglobulinemia: Monitor and consider immunoglobulin replacement therapy.

The most common adverse reactions (incidence ≥ 30%) in: • LBCL are fever, CRS, fatigue, musculoskeletal pain, and nausea. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decrease, neutrophil count decrease, platelet count decrease, and hemoglobin decrease. • CLL/SLL are CRS, encephalopathy, fatigue, musculoskeletal pain, nausea, edema and diarrhea. The most common Grade 3-4 laboratory abnormalities include neutrophil count decrease, white blood cell decrease, hemoglobin decrease, platelet count decrease, and lymphocyte count decrease. • FL are CRS. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decreased, neutrophil count decreased, and white blood cell decreased. • MCL are CRS, fatigue, musculoskeletal pain, and encephalopathy.

Drug-Laboratory Test Interactions HIV and the lentivirus used to make BREYANZI have limited, short spans of identical genetic material (RNA). Therefore, some commercial HIV nucleic acid tests may yield false-positive results in patients who have received BREYANZI.

Store vials in the vapor phase of liquid nitrogen (less than or equal to minus 130°C) in a temperature-monitored system. • Thaw BREYANZI prior to infusion.