Process: Smart from the start

Help outsmart LBCL with earlier use of Breyanzi® CAR T cell therapy1
Think Breyanzi next at the first sign of relapse.1
  • Consult with a CAR T cell therapy treatment center as soon as a patient relapses to prevent delays in care
The first step in the process is to select an appropriate patient for Breyanzi.
Early identification of appropriate patients and collaboration with a CAR T cell therapy treatment center are key.
CAR T center location
Initiation1
Once a potential patient is identified, the certified Breyanzi treatment center confirms the patient's eligibility, and the enrollment process is initiated.1
Because of the risk of CRS and neurologic toxicities, Breyanzi is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Breyanzi REMS.
Certified treatment centers have undergone safety management training and are enrolled in the Breyanzi Risk Evaluation and Mitigation Strategy (REMS) program. Once you find the most appropriate treatment center, your patient will be evaluated for enrollment.
Breyanzi is a one-time treatment with options to be administered in an inpatient or outpatient setting.1*
Additional support for referrers, transplanters, patients, and caregivers is accessible at celltherapy360.com to help patients along the treatment journey
Breyanzi is currently offered at certified treatment centers across the United States, and more may continue to be added
FIND A BREYANZI
TREATMENT CENTER
CAR, chimeric antigen receptor; LBCL, large B-cell lymphoma.
*Treatment process includes leukapheresis, manufacturing, administration, and adverse event monitoring. A single dose of Breyanzi is 90 to 110 × 106 CAR-positive viable T cells for LBCL after 1 line of therapy, and 50 to 110 × 106 for LBCL after 2 or more lines of therapy (consisting of 1:1 CAR-positive viable T cells of the CD8 and CD4 components), with each component supplied separately in 1 to 4 single-dose vials.
Breyanzi manufacturing1
Drip bag icon
LEUKAPHERESIS
T cells are collected via leukapheresis at a qualified center.1
CAR T cells icon
MANUFACTURING
Cells are sent to a manufacturing site for purification, engineering, and expansion delivering a defined ratio of CAR-positive viable T cells (consisting of 1:1 CD8 and CD4 components). Ensure that patients understand the risk (11%) of manufacturing failure. Rates of manufacturing failure in the commercial setting differ from rates in the clinical trial.1
CAR T cells infusion icon
INFUSION
Breyanzi is delivered as separate vials of CD8-positive and CD4-positive cells. Lymphodepletion chemotherapy (fludarabine 30 mg/m2/day and cyclophosphamide 300 mg/m2/day concurrently for 3 days) should be completed 2 to 7 days before administration of Breyanzi.1
A single dose of Breyanzi contains 50 to 110 × 106 CAR-positive viable T cells (consisting of 1:1 CAR-positive viable T cells of the CD8 and CD4 components). The manufacturing target dose is 100 × 106 CAR-positive viable T cells.
Physician is notified of estimated Breyanzi availability date, which is subject to change. Confirm availability before starting lymphodepletion.1
HCP icon
MONITORING
Monitor patients daily at a certified healthcare facility during the first week following infusion for signs and symptoms of CRS and neurologic toxicities.
Instruct patients to remain within proximity of the certified healthcare facility for at least 4 weeks following infusion.1
LEUKAPHERESIS T cells are collected via leukapheresis at a qualified center.1
MANUFACTURING Cells are sent to a manufacturing site for purification, engineering, and expansion delivering a defined ratio of CAR-positive viable T cells (consisting of 1:1 CD8 and CD4 components). Ensure that patients understand the risk (11%) of manufacturing failure. Rates of manufacturing failure in the commercial setting differ from rates in the clinical trial.1
INFUSION Breyanzi is delivered as separate vials of CD8-positive and CD4-positive cells. Lymphodepletion chemotherapy (fludarabine 30 mg/m2/day and cyclophosphamide 300 mg/m2/day concurrently for 3 days) should be completed 2 to 7 days before administration of Breyanzi.1
A single dose of Breyanzi is 90 to 110 × 106 CAR-positive viable T cells for LBCL after 1 line of therapy, and
50 to 110 × 106 for LBCL after 2 or more lines of therapy (consisting of 1:1 CAR-positive viable T cells of the CD8 and CD4 components). The manufacturing target dose is 100 × 106 CAR-positive viable T cells.1
Physician is notified of estimated Breyanzi availability date, which is subject to change. Confirm availability before starting lymphodepletion.
MONITORING Monitor patients daily at a certified healthcare facility during the first week following infusion for signs and symptoms of CRS and neurologic toxicities.
Instruct patients to remain within proximity of the certified healthcare facility for at least 4 weeks following infusion.1
Follow-up1
Post-infusion monitoring: After at least 4 weeks of post-infusion monitoring, patients require long-term monitoring and appointments.1
Advise your patients to avoid driving or operating heavy or potentially dangerous machines for at least 8 weeks following their Breyanzi infusion.1
  • Continue to monitor for signs and symptoms of CRS and NT. Evaluate and treat promptly
  • Continue to monitor CBC and watch for signs and symptoms of serious infections, febrile neutropenia, prolonged cytopenias, B-cell aplasia, hypogammaglobulinemia, and secondary malignancies
  • Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol Myers Squibb at 1-888-805-4555 for reporting and instructions
CAR, chimeric antigen receptor; CBC, complete blood counts; CRS, cytokine release syndrome; LBCL, large B-cell lymphoma; NT neurolgic toxicity.
HCP icon
Patients may be enrolled in the Breyanzi registry, which will monitor safety for up to 15 years. Patients should also be monitored lifelong for potential secondary malignancies
Breyanzi® is designed for gradual expansion* and persistence1
Smart engineering: Breyanzi is a CD19-directed CAR T cell therapy1
Breyanzi receptor icon
The 4-1BB co-stimulatory domain signaling enhances the expansion and persistence of Breyanzi.1
Defined and purified† product–defined composition reduces variability of the CD8 and CD4 component dose.1
CAR T cells drip bag icon
Breyanzi is administered as a one-time treatment.1‡
Breyanzi was present in the peripheral blood for up to 2 years1
Breyanzi binds to CD19 expressed on the cell surface of tumor and normal B cells, inducing activation of CAR T cells and killing target cells.1
The binding region of the CAR is composed of a CD19-directed, antibody-derived, single-chain variable fragment.1
CAR T binding icon
  1. Extracellular receptor-binding region
  2. IgG4 hinge region
  3. CD28 transmembrane domain
  4. The receptor is fused to intracellular signaling domains, including a 4-1BB co-stimulatory domain to enhance the expansion and persistence
  5. CD3 zeta activation domain
CAR, chimeric antigen receptor.
* The median time of maximal expansion in peripheral blood occurred 12 days after infusion.
† 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.
‡ Treatment process includes leukapheresis, manufacturing, administration, and adverse event monitoring. A single dose of Breyanzi contains 90 to 110 × 106 CAR-positive viable T cells for LBCL after 1 line of therapy, and 50 to 110 × 106 for LBCL after 2 or more lines of therapy (consisting of 1:1 CAR-positive viable T cells of the CD8 and CD4 components), with each component supplied separately in 1 to 4 single-dose vials.
Important Safety Information
LESS
Important Safety Information

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

  • 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.
  • 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.
  • BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.
CYTOKINE RELEASE SYNDROME
Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. Among patients receiving BREYANZI for LBCL (N=418), CRS occurred in 46% (190/418), including ≥ Grade 3 CRS (Lee grading system) in 3.1% of patients.
In patients receiving BREYANZI after two or more lines of therapy for LBCL, CRS occurred in 46% (122/268), including ≥ Grade 3 CRS in 4.1% of patients. One patient had fatal CRS and 2 had ongoing CRS at time of death. The median time to onset was 5 days (range: 1 to 15 days). CRS resolved in 98% with a median duration of 5 days (range: 1 to 17 days).
In patients receiving BREYANZI after one line of therapy for LBCL, CRS occurred in 45% (68/150), including Grade 3 CRS in 1.3% of patients. The median time to onset was 4 days (range: 1 to 63 days). CRS resolved in all patients with a median duration of 4 days (range: 1 to 16 days).
The most common manifestations of CRS (≥10%) included fever (94%), hypotension (42%), tachycardia (28%), chills (23%), hypoxia (16%), and headache (12%).
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).
Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI.
Of the 418 patients who received BREYANZI for LBCL, 23% received tocilizumab and/or a corticosteroid for CRS, including 10% who received tocilizumab only and 2.2% who received corticosteroids only.
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 patients receiving BREYANZI after two or more lines of therapy for LBCL, CAR T cell-associated neurologic toxicities occurred in 35% (95/268), including ≥ Grade 3 in 12% of patients. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death. The median time to onset of neurotoxicity was 8 days (range: 1 to 46 days). Neurologic toxicities resolved in 85% with a median duration of 12 days (range: 1 to 87 days).
In patients receiving BREYANZI after one line of therapy for LBCL, CAR T cell-associated neurologic toxicities occurred in 27% (41/150) of patients, including Grade 3 cases in 7% of patients. The median time to onset of neurologic toxicities was 8 days (range: 1 to 63 days). The median duration of neurologic toxicity was 6 days (range: 1 to 119 days).
In all patients combined receiving BREYANZI for LBCL, neurologic toxicities occurred in 33% (136/418), including ≥ Grade 3 cases in 10% of patients. The median time to onset was 8 days (range: 1 to 63), with 87% of cases developing by 16 days. Neurologic toxicities resolved in 85% of patients with a median duration of 11 days (range: 1 to 119 days). Of patients developing neurotoxicity, 77% (105/136) also developed CRS.
The most common neurologic toxicities (≥ 5%) included encephalopathy (20%), tremor (13%), aphasia (8%), headache (6%), dizziness (6%), and delirium (5%).
CRS AND NEUROLOGIC TOXICITIES MONITORING
Monitor patients daily for at least 7 days following BREYANZI infusion at a REMS-certified healthcare facility for signs and symptoms of CRS and neurologic toxicities and assess for other causes of neurological symptoms. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion and treat promptly. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Manage neurologic toxicity with supportive care and/or corticosteroid as needed. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time.
BREYANZI REMS
Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:
  • Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
  • Certified healthcare facilities must have on-site, immediate access to tocilizumab.
  • Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.
  • Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer BREYANZI are trained on the management of CRS and neurologic toxicities.
Further information is available at www.BreyanziREMS.com, or contact Bristol-Myers Squibb at 1-888-423-5436.
HYPERSENSITIVITY REACTIONS
Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).
SERIOUS INFECTIONS
Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion.
In patients receiving BREYANZI for LBCL, infections of any grade occurred in 36% with Grade 3 or higher infections occuring in 12% of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7%, bacterial infections occurred in 4.3%, viral infections in 1.9% and fungal infections in 0.5%.
Febrile neutropenia developed after BREYANZI infusion in 8% of patients with LBCL. 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.
In patients who received BREYANZI for LBCL, 15 of the 16 patients with a prior history of HBV were treated with concurrent antiviral suppressive therapy. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. In patients with prior history of HBV, consider concurrent antiviral suppressive therapy to prevent HBV reactivation per standard guidelines.
PROLONGED CYTOPENIAS
Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion.
Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 36% of patients with LBCL and included thrombocytopenia in 28%, neutropenia in 21%, and anemia in 6%.
Monitor complete blood counts prior to and after BREYANZI administration.
HYPOGAMMAGLOBULINEMIA
B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with BREYANZI.
In patients receiving BREYANZI for LBCL, hypogammaglobulinemia was reported as an adverse reaction in 11% of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 28% of patients.
Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.
Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI.
SECONDARY MALIGNANCIES
Patients treated with BREYANZI may develop secondary malignancies. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol-Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
Due to the potential for neurologic events, including altered mental status or seizures, patients receiving BREYANZI are at risk for developing altered or decreased consciousness or impaired coordination in the 8 weeks following BREYANZI administration. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, for at least 8 weeks.
ADVERSE REACTIONS
The most common nonlaboratory adverse reactions (incidence ≥ 30%) are fever, CRS, fatigue, musculoskeletal pain, and nausea.
The most common Grade 3-4 laboratory abnormalities (≥ 30%) include lymphocyte count decrease, neutrophil count decrease, platelet count decrease, and hemoglobin decrease.
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.
Indication
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 two or more lines of systemic therapy.
Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.
References
  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2023.
  2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V5.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed July 7, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org.
  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2023.
  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2023.
  2. Kamdar M, Solomon S, Arnason J, et al. Lisocabtagene maraleucel, a CD19-directed chimeric antigen receptor T cell therapy, versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma: results from the randomized phase 3 TRANSFORM study. Presented at the 63rd American Society of Hematology Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA.
  3. Data on file. BMS-REF-LIS-0016. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  4. Kamdar M, Solomon S, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from the randomized phase 3 interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399(10343):2294-2308.
  5. Abramson J, Solomon S, Arnason J, et al. Lisocabtagene maraleucel (liso-cel) versus standard of care (SOC) with salvage chemotherapy followed by autologous stem cell transplantation (ASCT) as second-line (2L) treatment in patients with relapsed or refractory large B-cell lymphoma (LBCL): primary analysis of the randomized, phase 3 transform study. Presented at the 64th American Society of Hematology Annual Meeting & Exposition; December 10-13, 2022; New Orleans, Louisiana.
  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2023.
  2. Sehgal A, Hoda D, Riedell P, et al. Lisocabtagene maraleucel as a second-line therapy for relapsed or refractory large B-cell lymphoma in patients not intended for hematopoietic stem cell transplantation: primary analysis from the phase 2 PILOT study. Presented at the American Society of Oncology Annual Meeting; June 3-7, 2022; Chicago, IL.
  3. Data on file. BMS-REF-LIS-0019. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2023.
  2. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396(10254):839-852.
  3. Data on file. TRANSCEND DOR. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  4. Abramson J, Palomba M, Gordon L, et al. Two-year follow-up of TRANSCEND NHL 001, a multicenter phase 1 study of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphomas. Presented at the 63rd American Society of Hematology Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA.
  5. Data on file. TRANSCEND CD19. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2023.
  2. Kamdar M, Solomon S, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399(10343):2294-2308.
  3. Abramson J, Palomba M, Gordon L, et al. Two-year follow-up of TRANSCEND NHL 001, a multicenter phase 1 study of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphomas. Presented at the 63rd American Society of Hematology Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA.

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