Lisocabtagene Maraleucel
FDA Drug Information • Also known as: Breyanzi
- Brand Names
- Breyanzi
- Dosage Form
- LIQUID
- Product Type
- BULK INGREDIENT
⚠ Boxed Warning (Black Box)
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 [see Dosage and Administration ( 2.2 , 2.3 ) and Warnings and Precautions ( 5.1 )] . Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed [see Dosage and Administration ( 2.2 , 2.3 ) and Warnings and Precautions ( 5.2 )] . T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI [see Warnings and Precautions ( 5.7 )] . WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, AND SECONDARY HEMATOLOGICAL MALIGNANCIES See full prescribing information for complete boxed warning. 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. ( 2.2 , 2.3 , 5.1 ) Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed. ( 2.2 , 2.3 , 5.2 ) T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI. ( 5.7 )Description
11 DESCRIPTION BREYANZI (lisocabtagene maraleucel) is a CD19-directed genetically modified autologous T cell immunotherapy administered as a defined composition of CAR-positive viable T cells (consisting of CD8 and CD4 components). The CAR is comprised of the 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. In addition, BREYANZI includes a nonfunctional truncated epidermal growth factor receptor (EGFRt) that is co-expressed on the cell surface with the CD19-specific CAR. BREYANZI is a T cell product. BREYANZI is prepared from the patient’s T cells, which are obtained via a standard leukapheresis procedure. The purified CD8-positive and CD4-positive T cells are separately activated and transduced with the replication-incompetent lentiviral vector containing the anti-CD19 CAR transgene. The transduced T cells are expanded in cell culture, washed, formulated into a suspension, and cryopreserved as separate CD8 and CD4 component vials that together constitute a single dose of BREYANZI. The product must pass a sterility test before release for shipping as a frozen suspension in patient-specific vials. The product is thawed prior to administration [see Dosage and Administration ( 2.2 ) and How Supplied/Storage and Handling ( 16 )] . The BREYANZI formulation contains 75% (v/v) Cryostor ® CS10 [containing 7.5% dimethylsulfoxide (v/v)], 24% (v/v) Multiple Electrolytes for Injection, Type 1, 1% (v/v) of 25% albumin (human).
What Is Lisocabtagene Maraleucel Used For?
1 INDICATIONS AND USAGE 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. ( 1.1 ) Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma. ( 1 , 14 ) adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). ( 1.2 ) adult patients with relapsed or refractory follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy. ( 1.3 ) adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. ( 1.4 ) adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least 2 prior lines of systemic therapy. ( 1.5 ) 1.1 Large B-cell Lymphoma (LBCL) BREYANZI is 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. Limitations of Use : BREYANZI is not indicated for the treatment of patients with primary central nervous system (CNS) lymphoma [see Clinical Studies ( 14.1 )]. 1.2 Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) BREYANZI is indicated for the treatment of...Dosage and Administration
2 DOSAGE AND ADMINISTRATION For autologous use only. For intravenous use only.
Do NOT use a leukodepleting filter. ( 2.2 ) Administer a lymphodepleting regimen of fludarabine and cyclophosphamide before infusion of BREYANZI. ( 2.2 ) Verify the patient’s identity prior to infusion. ( 2.2 ) Premedicate with acetaminophen and an H 1 antihistamine. ( 2.2 ) Confirm availability of tocilizumab prior to infusion. ( 2.2 , 5.1 ) Dosing of BREYANZI is based on the number of chimeric antigen receptor (CAR)-positive viable T cells. ( 2.1 ) For LBCL : after one line of therapy, the dose is 90 to 110 × 10 6 CAR-positive viable T cells. ( 2.1 ) after two or more lines of therapy, the dose is 50 to 110 × 10 6 CAR-positive viable T cells. ( 2.1 ) For CLL/SLL, FL, MCL and MZL : the dose is 90 to 110 × 10 6 CAR-positive viable T cells. ( 2.1 ) 2.1 Dose For autologous use only. For intravenous use only. See the respective Certificate of Release for Infusion (RFI Certificate) for each component, for the actual cell counts and volumes to be infused [see Dosage and Administration ( 2.2 ) and Dosage Forms and Strengths ( 3 )]. A single dose of BREYANZI contains CAR-positive viable T cells (consisting of 1:1 CAR-positive viable T cells of the CD8 and CD4 components), with each component supplied separately in one to four single-dose vials. See Table 1 for dose range per indication. Table 1: Dose Range Abbreviations: LBCL = large B-cell lymphoma; CLL = chronic lymphocytic leukemia; SLL = small lymphocytic lymphoma; FL = follicular lymphoma; MCL = mantle cell lymphoma; MZL = marginal zone lymphoma. Indication BREYANZI dose range LBCL after two or more lines of therapy ( 1.1 ) 50 to 110 × 10 6 CAR-positive viable T cells LBCL after one line of therapy ( 1.1 ) 90 to 110 × 10 6 CAR-positive viable T cells CLL or SLL ( 1.2 ) 90 to 110 × 10 6 CAR-positive viable T cells FL ( 1.3 ) 90 to 110 × 10 6 CAR-positive viable T cells MCL ( 1.4 ) 90 to 110 × 10 6 CAR-positive viable T cells MZL ( 1.5 ) 90 to 110 × 10 6 CAR-positive viable T cells 2.2 Administration BREYANZI is for autologous use only. The patient’s identity must match the patient identifiers on the BREYANZI cartons, vials, and syringe labels. Do not infuse BREYANZI if the information on the patient-specific labels does not match the intended patient. Preparing the Patient for BREYANZI Confirm the availability of BREYANZI before starting lymphodepleting chemotherapy. Pretreatment Administer the lymphodepleting chemotherapy regimen before infusion of BREYANZI: fludarabine 30 mg/m 2 /day intravenously (IV), and cyclophosphamide 300 mg/m 2 /day IV for 3 days. See the prescribing information for fludarabine and cyclophosphamide for information on dose adjustment in renal impairment. Infuse BREYANZI 2 to 7 days after completion of lymphodepleting chemotherapy. Delay the infusion of BREYANZI if the patient has unresolved serious adverse events from preceding chemotherapies, active uncontrolled infection, or...Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS 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. ( 6.1 ) 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. ( 6.1 ) FL are CRS. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decreased, neutrophil count decreased, and white blood cell decreased. ( 6.1 ) MCL are CRS, fatigue, musculoskeletal pain, and encephalopathy. The most common Grade 3-4 laboratory abnormalities include neutrophil count decrease, white blood cell decrease, and platelet count decrease. ( 6.1 ) MZL are CRS. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decreased, neutrophil count decreased, and white blood cell decreased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described in the WARNINGS and PRECAUTIONS and in this section reflects exposure to a single dose of BREYANZI in 769 patients in five clinical studies as described below. Study 1 (JCAR017-BCM-003; Relapsed or Refractory LBCL After One Line of Therapy) Study 1 was a randomized, open-label, multicenter study, in which patients with primary refractory LBCL or relapse within 1 year of first-line chemoimmunotherapy received BREYANZI (N=89) or standard therapy (N=91) [see Clinical Studies ( 14.1 )] . Patients had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous HSCT. The trial excluded patients who were ineligible for transplant or who had age > 75 years, Eastern Cooperative Oncology Group (ECOG) performance status >1, history of central nervous system (CNS) disorders (such as seizures or stroke), uncontrolled infection, CrCl < 45 mL/min, alanine aminotransferase (ALT) > 5 times the upper limit of normal (ULN), left ventricular ejection fraction (LVEF) < 40%, or absolute neutrophil count (ANC) < 1.0 × 10 9 cells/L or platelets < 50 × 10 9 cells/L in the absence of bone marrow involvement. The planned dose of BREYANZI was 100 × 10 6 CAR-positive viable T cells. The median age of the BREYANZI-treated population was 59 years (range: 20 to 74 years); 47% were male; 58% were White, 11% were Asian, and 5% were Black. Serious adverse reactions occurred in 38% of patients. The most common nonlaboratory serious adverse reactions (> 2%) were CRS, sepsis, fever, febrile neutropenia, headache, aphasia, COVID-19 infection, and pulmonary embolism. Table 4 presents selected nonlaboratory adverse reactions in patients treated with BREYANZI, and Table 5 describes selected new or worsening Grade 3 or 4 laboratory abnormalities. The most common nonlaboratory adverse reactions (≥ 20%) were fever, CRS, musculoskeletal pain, headache, fatigue, nausea, constipation, and dizziness. Table 4: Adverse Reactions in ≥ 10% of Patients with Relapsed or Refractory LBCL Treated with BREYANZI in Study 1 (N=89) * Represents multiple related terms. a Dizziness includes dizziness, dizziness postural, syncope, vertigo. b Motor dysfunction includes fine motor skill dysfunction, muscle spasms, muscular weakness. c Tremor includes resting tremor, tremor, essential tremor. d Hemorrhage includes conjunctival hemorrhage, cystitis hemorrhagic,...Drug Interactions
7 DRUG INTERACTIONS 7.1 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.
Contraindications
4 CONTRAINDICATIONS None. None. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no available data with BREYANZI use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with BREYANZI to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known if BREYANZI has the potential to be transferred to the fetus. Based on the mechanism of action, if the transduced cells cross the placenta, they may cause fetal toxicity, including B-cell lymphocytopenia and hypogammaglobulinemia. Therefore, BREYANZI is not recommended for women who are pregnant, and pregnancy after BREYANZI infusion should be discussed with the treating physician. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING BREYANZI consists of genetically modified autologous T cells, supplied in vials as separate frozen suspensions of each CD8 component (NDC 73153-901-08) and CD4 component (NDC 73153-902-04). Each CD8 or CD4 component is packed in a carton containing up to 4 vials, depending upon the concentration of the cryopreserved drug product CAR-positive viable T cells. The cartons for each CD8 component and CD4 component are in an outer carton (NDC 73153-900-01). BREYANZI is shipped directly to the cell lab or clinical pharmacy associated with the infusion center in the vapor phase of a liquid nitrogen shipper. A Release for Infusion (RFI) Certificate for each component and patient-specific syringe labels are affixed inside the shipper.
Confirm patient identity upon receipt. 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 [see Dosage and Administration ( 2.2 )] .About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.