Engage Breyanzi® CAR T cell therapy in your R/R CLL or SLL treatment process

Consider Breyanzi in R/R patients who have received 2 prior lines of therapy, including a BTKi and a BCL2-i1
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
*Treatment process includes leukapheresis, manufacturing, administration, and adverse event monitoring. A single dose of Breyanzi contains a target of 100 × 106 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 1 to 4 single-dose vials.
BCL-2i, B-cell lymphoma-2 inhibitor; BTKi, Bruton tyrosine kinase inhibitor; CAR, chimeric antigen receptor; CLL, chronic lymphocytic leukemia; CRS, cytokine release syndrome; MOA, mechanism of action; R/R, relapsed or refractory; SLL, small lymphocytic lymphoma.
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 contains 90 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.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; CLL, chronic lymphocytic leukemia; CRS, cytokine release syndrome; MOA, mechanism of action; NT, neurologic toxicity; R/R, relapsed or refractory; SLL, small lymphocytic lymphoma.
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 therapy
Breyanzi receptor icon
The 4-1BB co-stimulatory domain signaling enhances the expansion and persistence of Breyanzi.1
Defined and purified† product–defined ratio reduces variability of the CD8 and CD4 component
dose.1
CAR T cells drip bag icon
Breyanzi is administered as a one-time infusion.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
*The median time of maximal expansion in peripheral blood occurred 12 days after infusion.1
†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.1
‡Treatment process includes leukapheresis, manufacturing, administration, and adverse event monitoring. A single dose of Breyanzi contains a target of 100 × 106 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 1 to 4 single-dose vials.1
CAR, chimeric antigen receptor; CLL, chronic lymphocytic leukemia; MOA, mechanism of action; R/R, relapsed or refractory; SLL, small lymphocytic lymphoma.
Important Safety Information
LESS
Indication
BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy 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. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Important Safety Information

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.
  • 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.
  • T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI.
  • 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 CLL/SLL, CRS occurred in 83% (74/89), including Grade 3 CRS in 9% of patients. The median time to onset was 4 days (range: 1 to 18 days). CRS resolved in 97% with a median duration of 6 days (range: 2 to 37 days).
The most common manifestations of CRS (≥ 10%) included fever (97%), hypotension (46%), chills (43%), hypoxia (35%), sinus tachycardia (22%), and headache (18%).
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 patients who received BREYANZI for CLL/SLL (n=89), 64% received tocilizumab and/or a corticosteroid for CRS, including 33% 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 for CLL/SLL, CAR T cell-associated neurologic toxicities occurred in 46% (41/89), including Grade 3 cases in 20% of patients and a single Grade 4 case. The median time to onset of neurotoxicity was 7 days (range: 1 to 21 days), with 95% of cases developing by 16 days. Neurologic toxicities resolved in 85% with a median duration of 7 days (range: 1 to 83 days). Of patients developing neurotoxicity, 95% (39/41) also developed CRS.
The most common neurologic toxicities (≥ 5%) included encephalopathy (36%), tremor (14%), delirium (12%), headache (9%) and aphasia (8%).
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.
Further information is available at www.BreyanziREMS.com, or contact Bristol-Myers Squibb at 1-866-340- 7332.
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 CLL/SLL, infections of any grade occurred in 35%, with Grade 3 or higher infections occurring in 16% of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 10%, bacterial infections in 2.2%, fungal infections in 2.2%, and viral infections in 1.1%.
Febrile neutropenia developed after BREYANZI infusion in 12% of patients with CLL/SLL. 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 CLL/SLL, 9 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 45% of patients with CLL/SLL and included thrombocytopenia in 23%, neutropenia in 35%, and anemia in 12%. Monitor complete blood counts prior to and after BREYANZI administration.
Hypogammaglobulinemia
B-cell aplasia and hypogammaglobulinemia can occur in patients receiving BREYANZI. In patients receiving BREYANZI for CLL/SLL, hypogammaglobulinemia was reported as an adverse reaction in 14% of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 37% 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. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. 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.
Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS)
Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. Three of 89 (3%) safety evaluable patients with R/R CLL/SLL developed IEC-HS. Time to onset of IEC-HS ranged from 7 to 18 days. Two of the 3 patients developed IEC-HS in the setting of ongoing CRS and 1 in the setting of ongoing neurotoxicity. IEC-HS was fatal in 2 of 3 patients. One patient had fatal IEC-HS and one had ongoing IEC-HS at time of death. IEC-HS is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of IEC-HS should be administered per current practice guidelines.
Adverse Reactions
The most common nonlaboratory adverse reactions (incidence ≥ 30%) in CLL/SLL are cytokine release syndrome, encephalopathy, fatigue, musculoskeletal pain, nausea, and diarrhea. The most common Grade 3-4 laboratory abnormalities (≥ 30%) in CLL/SLL include neutrophil count decrease, white blood cell decrease, hemoglobin decrease, platelet count decrease, and lymphocyte count decrease.
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.
Reference
  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2024.

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Reference
  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2024.