Breyanzi®: A safety profile in R/R MCL you can count on that builds on evidence seen in clinical trials and other lymphoma indications1

The primary safety analysis was conducted in the full safety set (N=88), which included all patients who received a single dose of CAR-positive viable T cells.

3.2% Grade ≥3 CRS events reported in Breyanzi trials1

Majority of CRS events were low grade and most resolved quickly

Breyanzi grade of cytokine release syndrome (CRS) in TRANSCEND MCL Cohort Breyanzi grade of cytokine release syndrome (CRS) in TRANSCEND MCL Cohort

Breyanzi offers the flexibility of inpatient or outpatient administration for appropriate patients1

CRS-related clinical trial details (N=702)1
  • 29.5% of patients received tocilizumab and/or corticosteroids
    • 1.7% used corticosteroids only
    • 14.5% used tocilizumab only
    • Prophylactic systemic corticosteroids were not used in Breyanzi trials
  • CRS resolved in 98% of patients with a median duration of 5 (range 1-37) 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
  • In TRANSCEND MCL Cohort (N=88), 1.1% of patients experienced Grade ≥3 CRS
Cytokine release syndrome warnings and precautions1
  • CRS, including fatal or 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
  • 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
CAR, chimeric antigen receptor; CRS, cytokine release syndrome; MCL, mantle cell lymphoma; NT, neurologic toxicity; REMS, Risk Evaluation and Mitigation Strategy; R/R, relapsed or refractory.
10% Grade ≥3 NT in Breyanzi trials1

Majority of NT events were low grade and most resolved quickly

Breyanzi grade of neurologic toxicities (NT) in TRANSCEND MCL Cohort Breyanzi grade of neurologic toxicities (NT) in TRANSCEND MCL Cohort

Breyanzi offers the flexibility of inpatient or outpatient administration for appropriate patients1

NT-related clinical trial details (N=702)1
  • NTs resolved in 88% of cases with a median duration of 7 (range 1-119) days
  • 82% of patients with NT developed CRS
  • The most common NTs (≥5%) included encephalopathy, tremor, aphasia, delirium, and headache
Neurologic toxicity 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 NTs and assess for other causes of neurological symptoms. Monitor patients for signs or symptoms of NTs for at least 4 weeks after infusion and treat promptly. Manage NT with supportive care and/or corticosteroids as needed
  • Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time
CAR, chimeric antigen receptor; CRS, cytokine release syndrome; MCL, mantle cell lymphoma; NT, neurologic toxicity; REMS, Risk Evaluation and Mitigation Strategy; R/R, relapsed or refractory.
The most common adverse reactions observed in TRANSCEND MCL Cohort (N=88)1
  • Serious adverse reactions occurred in 53% of patients. The most common nonlaboratory serious adverse reactions (>2%) were CRS, confusional state, fever, encephalopathy, mental status changes, pleural effusion, upper respiratory tract infection, and decreased appetite. Fatal adverse reactions occurred in 4.5% of patients
    • One patient with MCL who received 3 prior lines of therapy developed a fatal case of cryptococcal meningoencephalitis 35 days after treatment with Breyanzi
  • The most common nonlaboratory adverse reactions (≥20%) were CRS, fatigue, musculoskeletal pain, encephalopathy, edema, headache, and decreased appetite
In clinical trials of Breyanzi (N=702)
  • Grade ≥3 infections occurred in 12% of patients. Infections of any grade were reported in 34% of patients
This table includes adverse reactions observed in ≥10% of the full population (N=88) in TRANSCEND MCL Cohort1
Adverse reactions* Any Grade (%) Grade 3 or higher (%)
Cardiac disorders
Tachycardiaa 17 3.4
Gastrointestinal disorders
Nausea 18 2.3
Diarrhea 17 0
Abdominal painb 15 3.4
Constipation 14 0
General disorders and administration site conditions
Fatiguec 39 2.3
Edemad 25 1.1
Fevere 17 0
Chills 11 0
Immune system disorders
Cytokine release syndrome 61 1.1
Infections and infestations
Infections with pathogen unspecifiedf 16 6
Upper respiratory tract infectiong 13 2.3
Metabolism and nutrition disorders
Decreased appetite 21 4.5
Musculoskeletal and connective tissue disorders
Musculoskeletal painh 38 2.3
Nervous system disorders
Encephalopathyi 30 9
Headache 23 0
Dizzinessj 11 2.3
Motor dysfunctionk 11 0
Tremor 11 0
Psychiatric disorders
Insomnial 14 0
Anxiety 13 1.1
Renal and urinary disorders
Renal failurem 15 0
Respiratory, thoracic, and mediastinal disorders
Dyspnean 11 0
Cough 10 0
Skin and subcutaneous tissue disorders
Rasho 11 1.1
Vascular disorders
Hypotensionp 15 0
Hemorrhageq 10 0
Hypertension 10 3.4

*Includes adverse reactions up to 90 days following treatment with Breyanzi.1

aTachycardia includes atrial fibrillation, sinus tachycardia, tachycardia, ventricular tachycardia.

bAbdominal pain includes abdominal discomfort, abdominal distension, abdominal pain, abdominal pain upper.

cFatigue includes asthenia, fatigue, malaise.

dEdema includes hypervolemia, localized edema, edema, edema peripheral, peripheral swelling, pleural effusion, pulmonary edema.

eFever includes pyrexia.

fGrouped per high-level grouped term.

gUpper respiratory tract infection includes nasal congestion, rhinitis, rhinorrhea, rhinovirus infection, upper respiratory tract infection.

hMusculoskeletal pain includes arthralgia, back pain, bone pain, musculoskeletal pain, myalgia, neck pain, pain in extremity.

iEncephalopathy includes confusional state, depressed level of consciousness, encephalopathy, lethargy, memory impairment, mental status changes, somnolence.

jDizziness includes dizziness, dizziness postural, syncope, vertigo.

kMotor dysfunction includes fine motor skill dysfunction, muscle spasms, muscle tightness, muscular weakness.

lInsomnia includes insomnia, sleep disorder.

mRenal failure includes acute kidney injury, blood creatinine increased.

nDyspnea includes dyspnea, tachypnea, wheezing.

oRash includes dermatitis contact, rash, rash erythematous, rash macular, rash maculo-papular, rash pruritic.

pHypotension includes hypotension, orthostatic hypotension.

qHemorrhage includes catheter site hemorrhage, epistaxis, hematoma, hematuria, hemorrhage, hemorrhoidal hemorrhage, rectal hemorrhage.

CRS, cytokine release syndrome; MCL, mantle cell lymphoma; NT, neurologic toxicity; R/R, relapsed or refractory.

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 mantle cell lymphoma (MCL) who have received at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor.
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 702 patients with non-Hodgkin lymphoma (NHL), CRS occurred in 54% of patients, including ≥ Grade 3 CRS in 3.2% of patients. The median time to onset was 5 days (range: 1 to 63 days). CRS resolved in 98% 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%) 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 88% of patients with a median duration of 7 days (range: 1 to 119 days). Of patients developing neurotoxicity, 82% 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 34% 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 3.7%, viral infections in 2%, and fungal infections in 0.7% of patients. One patient who received 4 prior lines of therapy developed a fatal case of John Cunningham (JC) virus progressive multifocal leukoencephalopathy 4 months after treatment with BREYANZI. One patient who received 3 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. In clinical trials of BREYANZI, 35 of 38 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 35% of patients, and included thrombocytopenia in 25%, neutropenia in 22%, and anemia in 6% 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 30% 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 MCL are cytokine release syndrome, 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.
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.