Breyanzi

Q: Who makes Breyanzi?

Breyanzi is listed by 1 labeler in the FDA NDC directory, including Juno Therapeutics, Inc..

Lisocabtagene maraleucel · Kit

Prescription (Rx)

Boxed warning. 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…

Uses

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 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 [see Clinical Studies ( 14.2 )] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). 1.3 Follicular Lymphoma (FL) BREYANZI is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy. 1.4 Mantle Cell Lymphoma (MCL) BREYANZI is indicated for the treatment of 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. 1.5 Marginal Zone Lymphoma (MZL) BREYANZI is indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least 2 prior lines of systemic therapy.

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 active graft-versus-host disease (GVHD). Premedication To minimize the risk of infusion reactions, premedicate the patient with acetaminophen (650 mg orally) and diphenhydramine (25-50 mg, IV or orally), or another H1-antihistamine, approximately 30 to 60 minutes prior to treatment with BREYANZI. Avoid prophylactic use of systemic corticosteroids, as they may interfere with the activity of BREYANZI. Receipt of BREYANZI
• BREYANZI is shipped directly to the cell-associated lab or clinical pharmacy associated with the infusion center in the vapor phase of a liquid nitrogen shipper.
• Confirm the patient’s identity with the patient identifiers on the shipper.
• If the patient is not expected to be ready for administration before the shipper expires and the infusion site is qualified for onsite storage, transfer BREYANZI to onsite vapor phase of liquid nitrogen storage prior to preparation.
• If the patient is not expected to be ready for administration before the shipper expires and the infusion site is not qualified for onsite storage, contact Bristol-Myers Squibb at 1-888-805-4555 to arrange for return shipment. Preparing BREYANZI Before thawing the vials
• Confirm the patient’s identity with the patient identifiers on the RFI Certificate.
• Read the RFI Certificate (affixed inside the shipper) for information on the number of syringes you will need to administer the CD8 and CD4 components (syringe labels are provided with the RFI Certificate). There is a separate RFI Certificate for each cell component.
• Confirm tocilizumab and emergency equipment are available prior to infusion and during the recovery period.
• Confirm the infusion time in advance and adjust the start time of BREYANZI thaw such that it will be available for infusion when the patient is ready. Thawing the vials 1. Confirm the patient’s identity with the patient identifiers on the outer carton and on the syringe labels. Once the vials of CAR-positive viable T cells (CD8 component and CD4 component) are removed from frozen storage, the thaw must be carried to completion and the cells administered within 2 hours. 2. Remove the CD8 component carton and CD4 component carton from the outer carton. 3. Confirm the patient’s identity with the patient identifiers on the inner carton. 4. Open each inner carton and visually inspect the vial(s) for damage. If the vials are damaged, contact Bristol-Myers Squibb at 1-888-805-4555. 5. Confirm the patient’s identity with the patient identifiers on the vials. 6. Carefully remove the vials from the cartons, place vials on a protective barrier pad, and thaw at room temperature until there is no visible ice in the vials. Thaw all of the vials at the same time. Keep the CD8 and CD4 components separate. Dose preparation
• Prepare BREYANZI using sterile technique.
• Based on the concentration of CAR-positive viable T cells for each component, more than one vial of each of the CD8 and CD4 components may be required to complete a dose.

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS BREYANZI is a cell suspension for infusion. A single dose of BREYANZI contains CAR-positive viable T cells that consist of CD8 and CD4 components, with each component supplied separately in single-dose vials [see Dosage and Administration ( 2.1 )] . More than one vial of each of the CD8 component and/or CD4 component may be needed to achieve the dose of BREYANZI. Each vial contains between 6.9 × 10 6 and 322 × 10 6 CAR-positive viable T cells in 4.6 mL cell suspension (between 1.5 × 10 6 and 70 x 10 6 CAR-positive viable T cells/mL). The infusion volume is calculated based on the concentration of cryopreserved drug product CAR-positive viable T cells. The volume may differ for each component infused. See the RFI Certificate for details [see How Supplied/Storage and Handling ( 16 )].
• BREYANZI is a cell suspension for infusion. ( 3 )
• A single dose of BREYANZI consists 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 5 mL vials. Each mL contains ≥ 1.5 × 10 6 to 70 × 10 6 CAR-positive viable T cells. ( 3 )

Contraindications

None. None. ( 4 )

Warnings and precautions

• Hypersensitivity Reactions: Monitor for hypersensitivity reactions during infusion. ( 5.3 )
• Serious Infections: Monitor patients for signs and symptoms of infection; treat appropriately. ( 5.4 )
• Prolonged Cytopenias: Patients may exhibit Grade 3 or higher cytopenias for several weeks following BREYANZI infusion. Monitor complete blood counts. ( 5.5 )
• Hypogammaglobulinemia: Monitor and consider immunoglobulin replacement therapy. ( 5.6 )
• Secondary Malignancies: T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI. In the event that a secondary malignancy occurs after treatment with BREYANZI, contact Bristol-Myers Squibb at 1-888-805-4555. ( 5.7 ) 5.1 Cytokine Release Syndrome Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. In clinical trials of BREYANZI, which included a total of 769 patients with non-Hodgkin lymphoma (NHL) exposed to BREYANZI, CRS occurred in 56% of patients, including ≥ Grade 3 CRS (Lee grading system 1 ) in 3.4% of patients. The median time to onset was 5 days (range: 1 to 63 days). CRS resolved in 99% of patients with a median duration of 5 days (range: 1 to 37 days). One patient had fatal CRS and 5 patients had ongoing CRS at the time of death. The most common manifestations of CRS (≥ 10%) included fever, hypotension, chills, tachycardia, hypoxia, and headache. Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) [see Adverse Reactions ( 6.1 )]. Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI. Monitor patients daily for at least 7 days following BREYANZI infusion for signs and symptoms of CRS. Continue to monitor patients for signs or symptoms of CRS for at least 2 weeks after infusion. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated [see Dosage and Administration ( 2.2 , 2.3 )] . Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time [see Patient Counseling Information ( 17 )]. 5.2 Neurologic Toxicities Neurologic toxicities that were fatal or life-threatening, including immune effector cell-associated neurotoxicity syndrome (ICANS), occurred following treatment with BREYANZI. Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, also occurred. In clinical trials of BREYANZI, CAR T cell-associated neurologic toxicities occurred in 32% of patients, including ≥ Grade 3 cases in 10% of patients. The median time to onset of neurotoxicity was 8 days (range: 1 to 63 days). Neurologic toxicities resolved in 88% of patients with a median duration of 7.5 days (range: 1 to 119 days). Of patients developing neurotoxicity, 83% also developed CRS. The most common neurologic toxicities (≥ 5%) included encephalopathy, tremor, aphasia, delirium, and headache. Monitor patients daily for at least 7 days following BREYANZI infusion for signs and symptoms of neurologic toxicities and assess for other causes of neurological symptoms. Continue to monitor patients for signs or symptoms of neurologic toxicities for at least 2 weeks after infusion and treat promptly. Manage neurologic toxicity with supportive care and/or corticosteroid as needed [see Dosage and Administration ( 2.2 , 2.3 )] . Advise patients to avoid driving for at least 2 weeks following infusion. Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time [see Patient Counseling Information ( 17 )] . 5.3 Hypersensitivity Reactions Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO). 5.4 Serious Infections Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion. In clinical trials of BREYANZI, infections of any grade occurred in 33% of patients, with Grade 3 or higher infections occurred in 12% of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7%, bacterial infections in 3.5%, viral infections in 2%, and fungal infections in 0.7% of patients. One patient with FL, who received four prior lines of therapy developed a fatal case of John Cunningham (JC) virus progressive multifocal leukoencephalopathy four months after treatment with BREYANZI. One patient with MCL, who received three prior lines of therapy, developed a fatal case of cryptococcal meningoencephalitis 35 days after treatment with BREYANZI. Febrile neutropenia developed after BREYANZI infusion in 8% of patients. Febrile neutropenia may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad‑spectrum antibiotics, fluids, and other supportive care as medically indicated. Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines. Avoid administration of BREYANZI in patients with clinically significant, active systemic infections. Viral Reactivation Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells.

Side effects

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, epistaxis, gastrointestinal hemorrhage, hematoma, hematuria, retinal hemorrhage, vaginal hemorrhage. Adverse Reaction Any Grade (%) Grade 3 or Higher (%) Blood and lymphatic system disorders Febrile neutropenia 10 10 Cardiac disorders Tachycardia * 15 1.1 Gastrointestinal disorders Nausea 24 0 Constipation 20 2.2 Diarrhea 18 0 Abdominal pain * 13 2.2 Vomiting 11 0 General disorders and administration site conditions Fever 55 3.4 Fatigue * 28 1.1 Edema * 13 0 Immune system disorders Cytokine release syndrome 49 1.1 Infections and infestations Bacterial infectious disorders * 12 6 Infections with pathogen unspecified * 12 6 Sepsis * 10 7 Metabolism and nutrition disorders Decreased appetite 15 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain * 36 3.4 Nervous system disorders Headache * 34 6 Dizziness a 20 1.1 Motor dysfunction b 12 3.4 Tremor c 11 1.1 Psychiatric disorders Insomnia * 15 0 Respiratory, thoracic, and mediastinal disorders Cough * 11 0 Skin and subcutaneous tissue disorders Rash * 12 1.1 Vascular disorders Hypotension * 15 2.2 Hemorrhage d 12 0 Other clinically important adverse reactions in < 10% of patients treated with BREYANZI included the following:
• Immune system disorders: Hemophagocytic lymphohistiocytosis (1.1%)
• Infections and infestations: Viral infection (9%), fungal infection (4.5%), pneumonia (2.2%)
• Nervous system disorders: Encephalopathy (8%), aphasia (4.5%), peripheral neuropathy (4.5%), ataxia (3.4%), paresis (1.1%)
• Psychiatric disorders: Delirium (2.2%)
• Renal and urinary disorders: Renal failure (3.4%)
• Respiratory, thoracic, and mediastinal disorders: Dyspnea (8%)
• Vascular disorders: Thrombosis (8%), hypertension (7%) Table 5: Grade 3 or 4 Laboratory Abnormalities Occurring in ≥ 10% of Patients with Relapsed or Refractory LBCL Treated with BREYANZI in Study 1 a Baseline lab values were assessed prior to lymphodepleting chemotherapy.

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.

Use in specific populations

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. 8.2 Lactation Risk Summary There is no information regarding the presence of BREYANZI in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BREYANZI and any potential adverse effects on the breastfed infant from BREYANZI or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Pregnancy status of females with reproductive potential should be verified. Sexually active females of reproductive potential should have a pregnancy test prior to starting treatment with BREYANZI. Contraception See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive lymphodepleting chemotherapy. There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with BREYANZI. Infertility There are no data on the effects of BREYANZI on fertility. 8.4 Pediatric Use The safety and efficacy of BREYANZI have not been established in pediatric patients. 8.5 Geriatric Use In clinical trials of BREYANZI, 111 (41%) of 268 patients with two or more prior lines of therapy for LBCL, and 89 (59%) of 150 patients with one prior line of therapy for LBCL, were 65 years of age or older; 27 (10%) and 28 (19%) were 75 years of age or older, respectively. In patients with CLL/SLL, 51 (57%) of 89 were 65 years of age or older, and 9 (10%) were 75 years of age or older. In patients with FL, 42 (39%) of 107 were 65 years of age or older, and 10 (9%) were 75 years of age or older. In patients with MCL, 64 (73%) of 88 patients were 65 years of age or older, and 18 (21%) were 75 years of age or older. In patients with MZL, 30 (45%) of 67 patients were 65 years of age or older, and 10 (15%) were 75 years of age or older. No clinically important differences in safety or effectiveness of BREYANZI were observed between patients aged ≥ 65 and younger patients.

Pregnancy

Pediatric use

8.4 Pediatric Use The safety and efficacy of BREYANZI have not been established in pediatric patients.

Geriatric use

8.5 Geriatric Use In clinical trials of BREYANZI, 111 (41%) of 268 patients with two or more prior lines of therapy for LBCL, and 89 (59%) of 150 patients with one prior line of therapy for LBCL, were 65 years of age or older; 27 (10%) and 28 (19%) were 75 years of age or older, respectively. In patients with CLL/SLL, 51 (57%) of 89 were 65 years of age or older, and 9 (10%) were 75 years of age or older. In patients with FL, 42 (39%) of 107 were 65 years of age or older, and 10 (9%) were 75 years of age or older. In patients with MCL, 64 (73%) of 88 patients were 65 years of age or older, and 18 (21%) were 75 years of age or older. In patients with MZL, 30 (45%) of 67 patients were 65 years of age or older, and 10 (15%) were 75 years of age or older. No clinically important differences in safety or effectiveness of BREYANZI were observed between patients aged ≥ 65 and younger patients.

Description

(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).

Mechanism of action

12.1 Mechanism of Action 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.

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 )] .

Patient information

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Ensure that patients understand the risk (11%) of manufacturing failure. In case of a manufacturing failure, a second manufacturing of BREYANZI may be attempted. While the patient awaits the product, additional bridging therapy (not the lymphodepletion) may be necessary. This bridging therapy may be associated with adverse events during the pre-infusion period, which could delay or prevent the administration of BREYANZI. Advise patients that they will be monitored daily for at least 7 days following the BREYANZI infusion and instruct patients to remain close to a healthcare facility for at least 2 weeks following the infusion. Prior to infusion, advise patients of the following risks:
• Cytokine Release Syndrome (CRS) – Signs and symptoms of CRS (fever, chills, hypotension, tachycardia, hypoxia, and fatigue). Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )].
• Neurologic Toxicities – Signs or symptoms associated with neurologic events including encephalopathy, confusion, decreased consciousness, speech disorders, tremor, and seizures. Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time [see Warnings and Precautions ( 5.2 ) and Adverse Reactions ( 6.1 )].
• Serious Infections – Signs or symptoms associated with infection [see Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.1 )] .
• Prolonged Cytopenias – Signs or symptoms associated with bone marrow suppression including neutropenia, anemia, thrombocytopenia, or febrile neutropenia [see Warnings and Precautions ( 5.5 ) and Adverse Reactions ( 6.1 )].
• Secondary Malignancies : Secondary malignancies, including T cell malignancies, have occurred [see Boxed Warning, Warnings and Precautions ( 5.7 ), Adverse Reactions ( 6.2 )]. Advise patients of the need to:
• Contact Bristol-Myers Squibb at 1-888-805-4555 if they are diagnosed with a secondary malignancy [see Warnings and Precautions ( 5.7 )] .
• Avoid driving for at least 2 weeks after BREYANZI administration .

Label text from the FDA structured product label by Juno Therapeutics, Inc. (revised Feb 20, 2026). Long sections are shortened; the complete label is on DailyMed.

Breyanzi NDC products (1)

NDC	Strength & form	Labeler	Type
73153-900	Kit	Juno Therapeutics, Inc.	BLA

Frequently asked questions

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Breyanzi is listed by 1 labeler in the FDA NDC directory, including Juno Therapeutics, Inc..