The safety profile for Breyanzi® in R/R FL builds on evidence seen in clinical trials and other lymphoma indications1

4% Grade ≥3 events reported in Breyanzi trials1
Breyanzi cytokine release syndrome (CRS) rates in TRANSCEND FL clinical trial, graph Breyanzi cytokine release syndrome (CRS) rates in TRANSCEND FL clinical trial, graph

The Breyanzi safety profile enables both inpatient and outpatient administration1

CRS-related clinical trial details
  • 30% (183/614) of patients received tocilizumab and/or corticosteroids for CRS1,2
    • Prophylactic systemic corticosteroids were not used in Breyanzi trials
    • 14% (87/614) received tocilizumab only
  • The most common manifestations of CRS (≥10%) were fever, hypotension, tachycardia, chills, hypoxia, and headache1
Cytokine release syndrome warnings and precautions1
  • CRS, including life-threatening reactions, occurred following treatment with Breyanzi
  • 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
  • Monitor patients daily for at least 7 days following Breyanzi infusion at a REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated
  • Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time

The majority of CRS events occurred early and resolved in <30 days2

CRS, cytokine release syndrome; FL, follicular lymphoma; REMS, Risk Evaluation and Mitigation Strategy.

10% Grade ≥3 NT events reported in Breyanzi trials1

The Breyanzi safety profile enables both inpatient and outpatient administration1

NT-related clinical trial details1
  • The most common neurologic toxicities (≥5%) included encephalopathy, tremor, aphasia, headache, dizziness, and delirium1
  • 81% of patients with NT also developed CRS1
Neurologic toxicities warnings and precautions1
  • NTs 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
  • Monitor patients daily for at least 7 days following Breyanzi infusion at a REMS-certified healthcare facility for signs and symptoms of neurologic toxicities and assess for other causes of neurological symptoms. Monitor patients for signs or symptoms of neurologic toxicities for at least 4 weeks after infusion and treat promptly. Manage neurologic toxicity with supportive care and/or corticosteroid as needed
  • Counsel patients to seek immediate medical attention should signs or symptoms of NT occur at any time

The majority of NT events occurred early and resolved in <30 days2

CRS, cytokine release syndrome; FL, follicular lymphoma; REMS, Risk Evaluation and Mitigation Strategy.
Predictable safety profile

The safety of Breyanzi was evaluated in the TRANSCEND FL study, in which 107 adult patients with R/R FL after 2 or more prior lines of therapy received a single dose of Breyanzi.

  • Serious adverse reactions occurred in 26% of patients. The most common nonlaboratory serious adverse reactions (>2%) were CRS, aphasia, febrile neutropenia, fever, and tremor
  • In TRANSCEND FL (N=107), the most common Any Grade nonlaboratory adverse reactions (≥20%) were CRS, headache, musculoskeletal pain, fatigue, constipation, and fever1
In clinical trials for Breyanzi (N=614):
  • Infections of Any Grade occurred in 33% of all patients
  • Infections of Grade 3 or higher occurred in 12% of all patients
    • One patient with FL, who received four prior lines of therapy developed a fatal case of John Cunningham (JC) virus progressive multifocal leukoencephalopathy 4 months after treatment with Breyanzi
  • Grade 3 or higher cytopenias persisted at Day 29 following Breyanzi infusion in 34% of patients, and included thrombocytopenia in 24%, neutropenia in 22%, and anemia in 7%
Adverse reactions in ≥10% of patients treated with Breyanzi in TRANSCEND FL (N=107)1
Adverse reactions* Any Grade (%) Grade 3 or higher (%)
Gastrointestinal disorders
Constipation 21 0
Diarrhea 15 0
General disorders and administration site conditions
Fatiguea 23 0
Feverb 20 0
Immune system disorders
Cytokine release syndrome 59 0.9
Infections and infestations
Infection with pathogen unspecifiedc 16 4.7
Musculoskeletal and connective tissue disorders
Musculoskeletal paind 28 0
Nervous system disorders
Headache 28 0
Tremor 15 0

*Includes adverse reactions up to 90 days following treatment with Breyanzi.

aFatigue includes asthenia, fatigue, somnolence.

bFever includes pyrexia.

cGrouped per high-level grouped term.

dMusculoskeletal pain includes arthralgia, back pain, bone pain, muscle spasms, flank pain, pain in extremity, myalgia, musculoskeletal pain, neck pain, muscle tightness, groin pain, tendonitis and ligament sprain.

AE, adverse event; CRS, cytokine release syndrome; FL, follicular lymphoma; NT, neurologic toxicity.

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 follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy. 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. In clinical trials of BREYANZI which enrolled a total of 614 patients with non-Hodgkin lymphoma (NHL), CRS occurred in 53% of patients, including Grade 3 or higher CRS in 4% of patients. The median time to onset was 5 days (range: 1 to 63 days). CRS resolved in 98% of patients with median duration of 5 days (range: 1 to 37 days). The most common manifestations of CRS (≥10%) were fever, hypotension, tachycardia, chills, 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).
Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI.
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 31% 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 87% of patients with a median duration of 8 days (range: 1 to 119 days). Of patients developing neurotoxicity, 81% also developed CRS.
The most common neurologic toxicities (≥5%) included encephalopathy, tremor, aphasia, headache, dizziness, and delirium.
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 clinical trials of BREYANZI, infections of any grade occurred in 33% of patients, with Grade 3 or higher infections occurring in 12% of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7%, bacterial infections in 4%, viral infections in 2%, and fungal infections in 0.7% of patients. One patient 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.
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. In clinical trials of BREYANZI, 26 of 29 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. In clinical trials of BREYANZI, Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 34% of patients, and included thrombocytopenia in 24%, neutropenia in 22%, and anemia in 7% of patients. Monitor complete blood counts prior to and after BREYANZI administration.
Hypogammaglobulinemia
B-cell aplasia and hypogammaglobulinemia can occur in patients receiving BREYANZI. In clinical trials of BREYANZI, hypogammaglobulinemia was reported as an adverse reaction in 10% of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 29% 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. 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 adverse reactions (incidence ≥30%) in FL are cytokine release syndrome. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decreased, neutrophil count decreased, and white blood cell decrease.
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.
Reference
  1. BREYANZI [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2024.
  2. Data on file. BMS-REF-LIS-0050. Princeton, NJ: Bristol-Myers Squibb Company; 2024.

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Reference
  1. BREYANZI [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2024.
  2. Data on file. BMS-REF-LIS-0050. Princeton, NJ: Bristol-Myers Squibb Company; 2024.