Safety

Breyanzi® has established safety and tolerability in a broad range of patients across trials1

Breyanzi was evaluated in 2L in TRANSFORM (N=89) and PILOT (N=61) and in 3L in TRANSCEND (N=268)1
Less than half of patients experienced Any Grade CRS1
Prophylactic corticosteroids were not used in Breyanzi trials.2
Occurrences were consistently low-grade and most resolved quickly across trials1
No Grade 4 or 5 CRS events were experienced in 2L trials2
In the TRANSCEND trial, one patient had fatal CRS and 2 had ongoing CRS at time of death.
Of the 418 patients who received Breyanzi for LBCL:
  • 23% received tocilizumab and/or a corticosteroid for CRS
  • 10% received tocilizumab only
  • 2.2% received corticosteroids only
  • Use of tocilizumab + corticosteroids were low
Most common manifestations of CRS (≥10%)1
Fever (94%), hypotension (42%), tachycardia (28%), chills (23%), hypoxia (16%), and headache (12%).
Cytokine release syndrome warnings and precautions1
  • Cytokine Release Syndrome (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
CRS, cytokine release syndrome; LBCL, large B-cell lymphoma.
Less than half of patients experienced Any Grade NT1
Occurrences were generally low-grade and most resolved quickly across trials1
No Grade 4 or 5 NT events were experienced in 2L trials2
Neurologic toxicities warnings and precautions1
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, have also occurred in patients treated with Breyanzi.
In TRANSCEND, three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death.
  • Monitor patients daily at least 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 neurologic toxicity occur at any time
Most common neurologic toxicities (≥5%)1
Encephalopathy (20%), tremor (13%), aphasia (8%), headache (6%), dizziness (6%) and delirium (5%).
NT, neurologic toxicities.
Breyanzi® adverse reactions observed across trials1
Incidence and severity of AEs were consistent across trials1
Adverse Reactions
Observed in at Least 10%
TRANSFORM Trial (N=89) PILOT Trial (N=61)
Any Grade (%) ≥Grade 3 (%) Any Grade (%) ≥Grade 3 (%)
Blood and lymphatic system disorders
Febrile neutropenia 10 10 - -
Cardiac disorders
Tachycardiaa,q,cc 15 1.1 10 -
Gastrointestinal disorders
Nausea 24 0 25 1.6
Constipation 20 2.2 11 0
Diarrhea 18 0 15 0
Abdominal painb,dd 13 2.2 - -
Vomiting 11 0 - -
General disorders and administration site conditions
Fever 55 3.4 38 1.6
Fatiguec,r,ee 28 1.1 44 2
Edemad,s,ff 13 0 20 -
Chills - - - -
Immune system disorders
Cytokine release syndrome 49 1.1 39 1.6
Infections and infestationse,gg
Bacterial infectious disorders 12 6 10 3.3
Infections—pathogen unspecifiedt,hh 12 6 13 4.9
Sepsisf 10 7 - -
Bacterial infection - - - -
Upper respiratory tract infection - - - -
Viral infection - - - -
Metabolism and nutrition disorders
Decreased appetite 15 0 13 1.6
Musculoskeletal and connective tissue disorders
Musculoskeletal pain g,v,kk 36 3.4 23 4.9
Motor dysfunctionh,ll 12 3.4 - -
Nervous system disorders
Headachei,mm 34 6 11 1.6
Dizzinessj,x,oo 20 1.1 16 1.6
Tremork,y,pp 11 1.1 16 0
Encephalopathyw,nn - - 23 4.9
Peripheral neuropathyqq - - - -
Aphasiarr - - - -
Psychiatric disorders
Insomnial,ss 15 0 11 0
Anxietytt - - - -
Deliriumuu - - - -
Renal and urinary disorders
Renal failurevv - - - -
Respiratory, thoracic, and mediastinal disorders
Coughm,z,ww 11 0 18 0
Dyspneaaa,xx - - 16 4.9
Skin and subcutaneous tissue disorders
Rashn,yy 12 1.1 - -
Vascular disorders
Hypotensiono,bb,zz 15 2.2 23 1.6
Hemorrhagep,aaa 12 0 - -
Hypertension - - 10 4.9
TRANSFORM
aTachycardia includes atrial flutter, sinus tachycardia, supraventricular tachycardia, tachycardia.
bAbdominal pain includes abdominal pain, abdominal pain lower, abdominal tenderness.
cFatigue includes asthenia, fatigue, malaise.
dEdema includes edema peripheral, localized edema, edema peripheral, pleural effusion swelling.
eInfections and infestations are grouped per high-level grouped term.
fSepsis includes bacteremia, bacterial sepsis, enterococcal bacteremia, Escherichia bacteremia, Klebsiella bacteremia, Klebsiella sepsis, sepsis, septic shock, staphylococcal bacteremia.
gMusculoskeletal pain includes arthralgia, back pain, bone pain, flank pain, musculoskeletal chest pain, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, osteoarthritis, pain in extremity.
hMotor dysfunction includes fine motor skill dysfunction, muscle spasms, muscular weakness.
iHeadache includes headache, migraine, migraine with aura.
jDizziness includes dizziness, dizziness postural, syncope, vertigo.
kTremor includes resting tremor, tremor, essential tremor.
lInsomnia includes insomnia, sleep disorder.
mCough includes cough, productive cough.
nRash includes catheter site rash, dermatitis acneiform, dermatitis exfoliative generalized, erythema multiforme, rash, rash maculo-papular, rash pruritic.
oHypotension includes hypotension, orthostatic hypotension.
pHemorrhage includes conjunctival hemorrhage, cystitis hemorrhagic, epistaxis, gastrointestinal hemorrhage, hematoma, hematuria, retinal hemorrhage, vaginal hemorrhage.
PILOT
qTachycardia includes atrial fibrillation, sinus tachycardia, tachycardia.
rFatigue includes asthenia, fatigue, malaise.
sEdema includes edema peripheral, pleural effusion, swelling.
tGrouped per high-level grouped term.
uUpper respiratory tract infection includes nasal congestion, paranasal sinus hypersecretion, rhinitis, rhinorrhea, upper respiratory tract infection.
vMusculoskeletal pain includes arthralgia, back pain, bone pain, flank pain, musculoskeletal chest pain, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, osteoarthritis, pain in extremity, spinal pain.
wEncephalopathy includes amnesia, apraxia, cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, dyscalculia, encephalopathy, lethargy, memory impairment, mental status changes, somnolence.
xDizziness includes dizziness, dizziness postural, syncope, vertigo.
yTremor includes resting tremor, tremor.
zCough includes cough, productive cough.
aaDyspnea includes acute respiratory distress syndrome, dyspnea, tachypnea, wheezing.
bbHypotension includes hypotension, orthostatic hypotension.
TRANSCEND
ccTachycardia includes heart rate increased, sinus tachycardia, tachycardia.
ddAbdominal pain includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness.
eeFatigue includes asthenia, fatigue, malaise.
ffEdema includes edema, edema peripheral, fluid overload, fluid retention, generalized edema, hypervolemia, peripheral swelling, pulmonary congestion, pulmonary edema, swelling.
ggInfections and infestations are grouped by pathogen type and selected clinical syndromes.
hhInfections with pathogen unspecified contains febrile neutropenia (9%).
iiBacterial infection includes infections by pathogen type plus appendicitis, diverticulitis, peritonitis, skin infection, tooth infection.
jj Upper respiratory tract infections include nasopharyngitis, pharyngitis, rhinitis, rhinovirus infection, sinusitis, upper respiratory tract congestion, upper respiratory tract infection.
kkMusculoskeletal pain includes arthralgia, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, pain in extremity, spinal pain.
llMotor dysfunction includes eyelid ptosis, motor dysfunction, muscle rigidity, muscle spasms, muscle spasticity, muscle tightness, muscle twitching, muscular weakness, myoclonus, myopathy.
mmHeadache includes headache, head discomfort, migraine, sinus headache.
nnEncephalopathy 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.
ooDizziness includes dizziness, presyncope, syncope, vertigo.
pTremor includes essential tremor, resting tremor, tremor.
rPeripheral neuropathy includes hyperesthesia, hypoesthesia, meralgia paresthetica, neuralgia, neuropathy peripheral, paresthesia, peripheral sensory neuropathy, sciatica, sensory loss.
rAphasia includes aphasia, disorganized speech, dysarthria, dysphemia, dysphonia, slow speech, speech disorder.
sInsomnia includes insomnia, somnambulism.
tAnxiety includes anxiety, panic attack.
uDelirium includes agitation, delirium, delusion, disorientation, hallucination, ‘hallucination, visual’, irritability, restlessness.
vRenal failure includes acute kidney injury, blood creatinine increased, chronic kidney disease, renal failure, renal injury.
wCough includes cough, productive cough, upper-airway cough syndrome.
xDyspnea includes acute respiratory failure, dyspnea, dyspnea exertional, respiratory failure.
yRash includes erythema, dermatitis acneiform, perineal rash, rash, rash erythematous, rash macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic, rash pustular.
zHypotension includes hypotension, orthostatic hypotension.
aaaHemorrhage includes catheter site hemorrhage, conjunctival hemorrhage, epistaxis, hematoma, hematuria, hemorrhage, hemorrhage intracranial, pulmonary hemorrhage, retinal hemorrhage, vaginal hemorrhage.
Adverse Reactions
Observed in at Least 10%
TRANSCEND Trial (N=268)
Any Grade (%) ≥Grade 3 (%)
Blood and lymphatic system disorders
Febrile neutropenia - -
Cardiac disorders
Tachycardiaa,q,c 25 0
Gastrointestinal disorders
Nausea 33 1.5
Constipation 23 0
Abdominal painb,dd 26 0.4
Diarrhea 21 3.0
Vomiting 21 0.4
General disorders and administration site conditions
Fever 16 0
Fatiguec,r,ee 48 3.4
Edemad,s,ff 21 1.1
Chills 12 0
Immune system disorders
Cytokine release syndrome 46 4.1
Hypogammaglobulinemiae - -
Infections and infestationse,gg
Bacterial infectious disorders - -
Infections—pathogen unspecifiedt,hh 29 16
Sepsisf - -
Bacterial infection 13 5
Upper respiratory tract infection 13 0.7
Viral infection 10 1.5
Metabolism and nutrition disorders
Decreased appetite 28 2.6
Musculoskeletal and connective tissue disorders
Musculoskeletal paing,v,kk 37 2.2
Motor dysfunctionh,ll 10 1.1
Nervous system disorders
Headachei,mm 30 1.1
Dizzinessj,x,oo 24 2.6
Tremork,y,pp 16 0
Encephalopathyw,nn 29 9
Peripheral neuropathyqq 11 0
Aphasiarr 10 2.2
Psychiatric disorders
Insomnial,ss 14 0.4
Anxietytt 10 0
Deliriumuu 10 2.2
Renal and urinary disorders
Renal failurevv 11 3.0
Respiratory, thoracic, and mediastinal disorders
Cough m,z,ww 23 0
Dyspneaa,xx 16 2.6
Skin and subcutaneous tissue disorders
Rashn,yy 13 0.4
Vascular disorders
Hypotensiono,bb,zz 26 3.4
Hemorrhagep,aaa 14 4.5
Hypertension 10 1.5
TRANSFORM
aTachycardia includes atrial flutter, sinus tachycardia, supraventricular tachycardia, tachycardia.
bAbdominal pain includes abdominal pain, abdominal pain lower, abdominal tenderness.
cFatigue includes asthenia, fatigue, malaise.
dEdema includes edema peripheral, localized edema, edema peripheral, pleural effusion swelling.
eInfections and infestations are grouped per high-level grouped term.
fSepsis includes bacteremia, bacterial sepsis, enterococcal bacteremia, Escherichia bacteremia, Klebsiella bacteremia, Klebsiella sepsis, sepsis, septic shock, staphylococcal bacteremia.
gMusculoskeletal pain includes arthralgia, back pain, bone pain, flank pain, musculoskeletal chest pain, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, osteoarthritis, pain in extremity.
hMotor dysfunction includes fine motor skill dysfunction, muscle spasms, muscular weakness.
iHeadache includes headache, migraine, migraine with aura.
jDizziness includes dizziness, dizziness postural, syncope, vertigo.
kTremor includes resting tremor, tremor, essential tremor.
lInsomnia includes insomnia, sleep disorder.
mCough includes cough, productive cough.
nRash includes catheter site rash, dermatitis acneiform, dermatitis exfoliative generalized, erythema multiforme, rash, rash maculo-papular, rash pruritic.
oHypotension includes hypotension, orthostatic hypotension.
pHemorrhage includes conjunctival hemorrhage, cystitis hemorrhagic, epistaxis, gastrointestinal hemorrhage, hematoma, hematuria, retinal hemorrhage, vaginal hemorrhage.
PILOT
qTachycardia includes atrial fibrillation, sinus tachycardia, tachycardia.
rFatigue includes asthenia, fatigue, malaise.
sEdema includes edema peripheral, pleural effusion, swelling.
tGrouped per high-level grouped term.
uUpper respiratory tract infection includes nasal congestion, paranasal sinus hypersecretion, rhinitis, rhinorrhea, upper respiratory tract infection.
vMusculoskeletal pain includes arthralgia, back pain, bone pain, flank pain, musculoskeletal chest pain, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, osteoarthritis, pain in extremity, spinal pain.
wEncephalopathy includes amnesia, apraxia, cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, dyscalculia, encephalopathy, lethargy, memory impairment, mental status changes, somnolence.
xDizziness includes dizziness, dizziness postural, syncope, vertigo.
yTremor includes resting tremor, tremor.
zCough includes cough, productive cough.
aaDyspnea includes acute respiratory distress syndrome, dyspnea, tachypnea, wheezing.
bbHypotension includes hypotension, orthostatic hypotension.
TRANSCEND
ccTachycardia includes heart rate increased, sinus tachycardia, tachycardia.
ddAbdominal pain includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness.
eeFatigue includes asthenia, fatigue, malaise.
ffEdema includes edema, edema peripheral, fluid overload, fluid retention, generalized edema, hypervolemia, peripheral swelling, pulmonary congestion, pulmonary edema, swelling.
ggInfections and infestations are grouped by pathogen type and selected clinical syndromes.
hhInfections with pathogen unspecified contains febrile neutropenia (9%).
iiBacterial infection includes infections by pathogen type plus appendicitis, diverticulitis, peritonitis, skin infection, tooth infection.
jj Upper respiratory tract infections include nasopharyngitis, pharyngitis, rhinitis, rhinovirus infection, sinusitis, upper respiratory tract congestion, upper respiratory tract infection.
kkMusculoskeletal pain includes arthralgia, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, pain in extremity, spinal pain.
llMotor dysfunction includes eyelid ptosis, motor dysfunction, muscle rigidity, muscle spasms, muscle spasticity, muscle tightness, muscle twitching, muscular weakness, myoclonus, myopathy.
mmHeadache includes headache, head discomfort, migraine, sinus headache.
nnEncephalopathy 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.
ooDizziness includes dizziness, presyncope, syncope, vertigo.
pTremor includes essential tremor, resting tremor, tremor.
rPeripheral neuropathy includes hyperesthesia, hypoesthesia, meralgia paresthetica, neuralgia, neuropathy peripheral, paresthesia, peripheral sensory neuropathy, sciatica, sensory loss.
rAphasia includes aphasia, disorganized speech, dysarthria, dysphemia, dysphonia, slow speech, speech disorder.
sInsomnia includes insomnia, somnambulism.
tAnxiety includes anxiety, panic attack.
uDelirium includes agitation, delirium, delusion, disorientation, hallucination, ‘hallucination, visual’, irritability, restlessness.
vRenal failure includes acute kidney injury, blood creatinine increased, chronic kidney disease, renal failure, renal injury.
wCough includes cough, productive cough, upper-airway cough syndrome.
xDyspnea includes acute respiratory failure, dyspnea, dyspnea exertional, respiratory failure.
yRash includes erythema, dermatitis acneiform, perineal rash, rash, rash erythematous, rash macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic, rash pustular.
zHypotension includes hypotension, orthostatic hypotension.
aaaHemorrhage includes catheter site hemorrhage, conjunctival hemorrhage, epistaxis, hematoma, hematuria, hemorrhage, hemorrhage intracranial, pulmonary hemorrhage, retinal hemorrhage, vaginal hemorrhage.
No new safety signals observed in 2L trials2
Most common adverse reactions across Breyanzi trials1
The most common nonlaboratory, serious adverse reactions (>2%) were CRS, febrile neutropenia, pulmonary embolism, headache, muscular weakness, aphasia, confusional state, gastrointestinal hemorrhage, encephalopathy, sepsis, pneumonia, fever, hypotension, dizziness, delirium, COVID-19 infection, and musculoskeletal pain.1
The most common nonlaboratory, adverse reactions of Any Grade (≥20%) were CRS, musculoskeletal pain, headache, fatigue, nausea, fever, constipation, dizziness, encephalopathy, hypotension, edema, infections (pathogen unspecified), decreased appetite, diarrhea, tachycardia, cough, abdominal pain, and vomiting.1
  • Serious adverse reactions occurred in 38% of patients in TRANSFORM and 33% in PILOT1
  • In the TRANSCEND trial, serious adverse reactions occurred in 46% of patients. Fatal adverse reactions occurred in 4% of patients1
Few Breyanzi patients experienced Any Grade AEs (17%) after the 90 day post-treatment emergent period (Grade ≥3, 8%).3
AE, adverse event; CRS, cytokine release syndrome.

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