For questions about BMS medicines during this time please call 1-800-721-8909.

BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma after two or more lines of systemic therapy, 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.
Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.

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Breyanzi Rates of Cytokine Release Syndrome (CRS) and Neurologic Toxicities (NT) (N=268)

Breyanzi® safety: evaluated in the largest pivotal trial in 3L+ large B-cell lymphoma (N=268)1,2

Breyanzi rates of cytokine release syndrome (CRS) (N=268)1*

Graphic depicting Breyanzi rates of cytokine release syndrome (CRS) (N=268) Graphic depicting Breyanzi rates of cytokine release syndrome (CRS) (N=268)

Tocilizumab and/or corticosteroid usage (23%)1

  • 10% received tocilizumab only
  • 9% received tocilizumab and a corticosteroid
  • 3% received corticosteroids only

CRS, including fatal or life-threatening reactions, occurred following treatment with Breyanzi.

Monitor patients daily at a certified healthcare facility during the first week following infusion for signs and symptoms of CRS.

  • Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion
  • Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time
  • At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated
  • Ensure that 2 doses of tocilizumab are available for each patient prior to infusion of Breyanzi

CRS was mostly low-grade. 41% experienced Grade 1 or Grade 2 (111/268)1

* Lee criteria for grading CRS (Lee et al, 2014).3
One patient had fatal CRS and 2 had ongoing CRS at time of death.

Breyanzi rates of neurologic toxicities (NT) (N=268)1*

Graphic depicting Breyanzi rates of neurologic toxicities (NT) (N=268) Graphic depicting Breyanzi rates of neurologic toxicities (NT) (N=268)

Prophylactic antiseizure medication was administered in 46% of patients (124/268).4

Onset of all NT occurred within the first 8 weeks1

  • 14% (38/268) received corticosteroids4

Neurologic toxicities that were fatal or life-threatening occurred following treatment with Breyanzi. 82% (78/95) of patients with NT experienced CRS. NT overlapped with CRS in 57 patients.

Monitor patients daily at a certified healthcare facility during the first week following infusion for signs and symptoms of neurologic toxicities.

  • Monitor patients for signs or symptoms of neurologic toxicities for at least 4 weeks after infusion; evaluate and treat promptly
  • Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time

NT was mostly low-grade. 24% experienced Grade 1 or Grade 2 (64/268)1

* NCI CTCAE version 4.03 criteria for grading neurologic toxicities.
Onset of first event.
Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death.

Summary of adverse reactions observed in at least 10% of the patients treated with Breyanzi in the TRANSCEND trial (N=268)1

Adverse reaction Any Grade (%) Grade 3 or higher (%)
Cardiac disorders    
Tachycardiaa 25 0
Gastrointestinal disorders    
Nausea 33 1.5
Diarrhea 26 0.4
Constipation 23 0
Abdominal painb 21 3
Vomiting 21 0.4
General disorders and administration site conditions    
Fatiguec 48 3.4
Edemad 21 1.1
Fever 16 0
Chills 12 0
Immune system disorders    
Cytokine release syndrome 46 4.1
Hypogammaglobulinemiae 32 0
Infections and infestationsf    
Infections—pathogen unspecifiedg 29 16
Bacterial infectious disordersh 13 5
Upper respiratory tract infectioni 13 0.7
Viral infectious disorders 10 1.5
Metabolism and nutrition disorders    
Decreased appetite 28 2.6
Musculoskeletal and connective tissue disorders    
Musculoskeletal painj 37 2.2
Motor dysfunctionk 10 1.1
Nervous system disorders    
Headachel 30 1.1
Encephalopathym 29 9
Dizzinessn 24 2.6
Tremoro 16 0
Peripheral neuropathyp 11 0
Aphasiaq 10 2.2
Psychiatric disorders    
Insomniar 14 0.4
Anxietys 10 0
Deliriumt 10 2.2
Renal and urinary disorders    
Renal failureu 11 3
Respiratory, thoracic, and mediastinal disorders    
Coughv 23 0
Dyspneaw 16 2.6
Skin and subcutaneous tissue disorders    
Rashx 13 0.4
Vascular disorders    
Hypotensiony 26 3.4
Hypertension 14 4.5
Hemorrhagez 10 1.5

a Tachycardia includes heart rate increased, sinus tachycardia, tachycardia.
b Abdominal pain includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness.
c Fatigue includes asthenia, fatigue, malaise.
d Edema includes edema, edema peripheral, fluid overload, fluid retention, generalized edema, hypervolemia, peripheral swelling, pulmonary congestion, pulmonary edema, swelling.
e Hypogammaglobulinemia includes subjects with adverse events of hypogammaglobulinemia (14%) and/or laboratory IgG levels that fell below 500 mg/dL after infusion (21%).
f Infections and infestations are grouped by pathogen type and selected clinical syndromes.
g Infections—pathogen unspecified unspecified contains febrile neutropenia (9%).
h Bacterial infection includes infections by pathogen type plus appendicitis, diverticulitis, peritonitis, skin infection, tooth infection.
i Upper respiratory tract infections include nasopharyngitis, pharyngitis, rhinitis, rhinovirus infection, sinusitis, upper respiratory tract congestion, upper respiratory tract infection.
j Musculoskeletal pain includes arthralgia, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, pain in extremity, spinal pain.
k Motor dysfunction includes eyelid ptosis, motor dysfunction, muscle rigidity, muscle spasms, muscle spasticity, muscle tightness, muscle twitching, muscular weakness, myoclonus, myopathy.
l Headache includes headache, head discomfort, migraine, sinus headache.
m Encephalopathy includes amnesia, bradyphrenia, cognitive disorder, confusional state, depersonalization/derealization disorder, depressed level of consciousness, disturbance in attention, encephalopathy, flat affect, hypersomnia, incoherent, lethargy, leukoencephalopathy, loss of consciousness, memory impairment, mental impairment, mental status changes, somnolence.
n Dizziness includes dizziness, presyncope, syncope, vertigo.
o Tremor includes essential tremor, resting tremor, tremor.
p Peripheral neuropathy includes hyperesthesia, hypoesthesia, meralgia paresthetica, neuralgia, neuropathy peripheral, paresthesia, peripheral sensory neuropathy, sciatica, sensory loss.
q Aphasia includes aphasia, disorganized speech, dysarthria, dysphemia, dysphonia, slow speech, speech disorder.
r Insomnia includes insomnia, somnambulism.
s Anxiety includes anxiety, panic attack.
t Delirium includes agitation, delirium, delusion, disorientation, hallucination, ‘hallucination, visual,’ irritability, restlessness.
u Renal failure includes acute kidney injury, blood creatinine increased, chronic kidney disease, renal failure, renal injury.
v Cough includes cough, productive cough, upper-airway cough syndrome.
w Dyspnea includes acute respiratory failure, dyspnea, dyspnea exertional, respiratory failure.
x Rash includes erythema, dermatitis acneiform, perineal rash, rash, rash erythematous, rash macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic, rash pustular.
y Hypotension includes hypotension, orthostatic hypotension.
z Hemorrhage includes catheter site hemorrhage, conjunctival hemorrhage, epistaxis, hematoma, hematuria, hemorrhage, hemorrhage intracranial, pulmonary hemorrhage, retinal hemorrhage, vaginal hemorrhage.

Grade 3 or 4 treatment-emergent laboratory abnormalities occurring in ≥10% of patients following treatment with Breyanzi based on CTCAE (N=268)1*

Bar chart showing rate of grade 3 or 4 treatment-emergent laboratory abnormalities Bar chart showing rate of grade 3 or 4 treatment-emergent laboratory abnormalities

* National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Treatment-emergent laboratory abnormalities are defined as data collected until Day 29.

Most common nonlaboratory serious adverse reactions (>2%):

CRS, encephalopathy, sepsis, febrile neutropenia, aphasia, pneumonia, fever, hypotension, dizziness, and delirium.1

Serious adverse reactions occurred in 46% of patients. Fatal adverse reactions occurred in 4% of patients.1

Most common nonlaboratory adverse reactions of any grade (≥20%):

Fatigue, CRS, musculoskeletal pain, nausea, headache, encephalopathy, infections (pathogen unspecified), decreased appetite, diarrhea, hypotension, tachycardia, dizziness, cough, constipation, abdominal pain, vomiting, and edema.1

AR, adverse reaction; CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events; DLBCL, diffuse large B-cell lymphoma; NCI, National Cancer Institute; NT, neurologic toxicities.

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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.

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 (CRS)

CRS, including fatal or life-threatening reactions, occurred following treatment with BREYANZI. CRS occurred in 46% (122/268) of patients receiving BREYANZI, including ≥ Grade 3 (Lee grading system) CRS in 4% (11/268) 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 119 of 122 patients (98%) with a median duration of 5 days (range: 1 to 17 days). Median duration of CRS was 5 days (range 1 to 30 days) in all patients, including those who died or had CRS ongoing at time of death.

Among patients with CRS, the most common manifestations of CRS include fever (93%), hypotension (49%), tachycardia (39%), chills (28%), and hypoxia (21%). 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.

Sixty-one of 268 (23%) patients received tocilizumab and/or a corticosteroid for CRS after infusion of BREYANZI. Twenty-seven (10%) patients received tocilizumab only, 25 (9%) received tocilizumab and a corticosteroid, and 9 (3%) received corticosteroids only.

Neurologic Toxicities

Neurologic toxicities that were fatal or life-threatening, occurred following treatment with BREYANZI. CAR T cell-associated neurologic toxicities occurred in 35% (95/268) of patients receiving BREYANZI, including ≥ Grade 3 in 12% (31/268) of patients. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death. The median time to onset of the first event was 8 days (range: 1 to 46 days). The onset of all neurologic events occurred within the first 8 weeks following BREYANZI infusion. Neurologic toxicities resolved in 81 of 95 patients (85%) with a median duration of 12 days (range: 1 to 87 days). Three of four patients with ongoing neurologic toxicity at data cutoff had tremor and one subject had encephalopathy. Median duration of neurologic toxicity was 15 days (range: 1 to 785 days) in all patients, including those with ongoing neurologic events at the time of death or at data cutoff.

Seventy-eight (78) of 95 (82%) patients with neurologic toxicity experienced CRS. Neurologic toxicity overlapped with CRS in 57 patients. The onset of neurologic toxicity was after onset of CRS in 30 patients, before CRS onset in 13 patients, same day as CRS onset in 7 patients, and same day as CRS resolution in 7 patients. Neurologic toxicity resolved in three patients before the onset of CRS. Eighteen patients experienced neurologic toxicity after resolution of CRS.

The most common neurologic toxicities included encephalopathy (24%), tremor (14%), aphasia (9%), delirium (7%), headache (7%), dizziness (6%), and ataxia (6%). Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, have occurred in patients treated with BREYANZI.

CRS and Neurologic Toxicities Monitoring

Monitor patients daily at a certified healthcare facility during the first week following infusion, for signs and symptoms of CRS and neurologic toxicities. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion; evaluate and treat promptly. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

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. Infections (all grades) occurred in 45% (121/268) of patients. Grade 3 or higher infections occurred in 19% of patients. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections occurred in 5%, and viral and fungal infections occurred in 1.5% and 0.4% of patients, respectively. Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines.

Febrile neutropenia has been observed in 9% (24/268) of patients after BREYANZI infusion and 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.

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. Ten of the 11 patients in the TRANSCEND study with a prior history of HBV were treated with concurrent antiviral suppressive therapy to prevent HBV reactivation during and after treatment with BREYANZI. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

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 31% (84/268) of patients, and included thrombocytopenia (26%), neutropenia (14%), and anemia (3%). Monitor complete blood counts prior to and after BREYANZI administration.

Hypogammaglobulinemia

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with BREYANZI. The adverse event of hypogammaglobulinemia was reported as an adverse reaction in 14% (37/268) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 21% (56/268) of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 32% (85/268) 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 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, during this initial period.

Adverse Reactions

Serious adverse reactions occurred in 46% of patients. The most common nonlaboratory, serious adverse reactions (> 2%) were CRS, encephalopathy, sepsis, febrile neutropenia, aphasia, pneumonia, fever, hypotension, dizziness, and delirium. Fatal adverse reactions occurred in 4% of patients.

The most common nonlaboratory adverse reactions of any grade (≥ 20%) were fatigue, CRS, musculoskeletal pain, nausea, headache, encephalopathy, infections (pathogen unspecified), decreased appetite, diarrhea, hypotension, tachycardia, dizziness, cough, constipation, abdominal pain, vomiting, and edema.

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 relapsed or refractory (R/R) large B-cell lymphoma after two or more lines of systemic therapy, 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.

Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.

References

  1. Breyanzi [prescribing information]. Bothell, WA; Juno Therapeutics, Inc., a Bristol Myers Squibb Company. 2021.
  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. Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124:188-195.
  4. Data on file. Juno Therapeutics, Inc., a Bristol Myers Squibb Company. 2021.