Table 3 : ( Continued )
Summary of Adverse Reactions Observed in at Least 10 % of the Patients Treated with BREYANZI ( lisocabtagene maraleucel ) in the TRANSCEND Study ( N = 268 )
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 paraesthetica , 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 maculopapular , 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 .
Other clinically important adverse reactions that occurred in less than 10 % of patients treated with BREYANZI include the following :
• Blood and lymphatic system disorders : Coagulopathy ( 1.5 %)
• Cardiac disorders : Arrhythmia ( 6 %), cardiomyopathy ( 1.5 %)
• Gastrointestinal disorders : Gastrointestinal hemorrhage ( 4.1 %)
• Infections and infestations : Pneumonia ( 8 %), fungal infections ( 8 %), sepsis ( 4.5 %), urinary tract infection ( 4.1 %)
• Injury , poisoning , and procedural complications : Infusion-related reaction ( 1.9 %)
• Metabolism and nutrition disorders : Tumor lysis syndrome ( 0.7 %)
• Nervous system disorders : Ataxia / gait disturbance ( 7 %), visual disturbance ( 5 %), paresis ( 2.6 %), cerebrovascular events ( 1.9 %), seizure ( 1.1 %), brain edema ( 0.4 %)
• Respiratory , thoracic , and mediastinal disorders : Pleural effusion ( 7 %), hypoxia ( 6 %)
• Vascular disorder : Thrombosis ( 7 %)
Table 4 :
Grade 3 or 4 Treatment Emergent Laboratory Abnormalities Occurring in ≥ 10 % of Patients Following Treatment with BREYANZI in the TRANSCEND Study a ( N = 268 )
Laboratory Abnormality Grade 3 or 4 (%) Neutropenia 76 Thrombocytopenia 39 Anemia 23 Hypofibrinogenemia 15 Hypophosphatemia 13 a NCI CTCAE = Common Terminology Criteria for Adverse Events version 4.03 .
Immunogenicity
BREYANZI has the potential to induce anti-product antibodies . The immunogenicity of BREYANZI has been evaluated using an electrochemiluminescence ( ECL ) immunoassay for the detection of binding antibodies against the extracellular CD19-binding domain of BREYANZI . Pre-existing anti-product antibodies were detected in 11 % ( 28 / 261 ) of patients . Treatment-induced or treatment-boosted anti-product antibodies were detected in 11 % ( 27 / 257 ) of patients . Due to the small number of patients who had anti-product antibodies , the relationship between anti-product antibody status and efficacy , safety , or pharmacokinetics was not conclusive .
DRUG INTERACTIONS
Drug-laboratory Test Interactions
HIV and the lentivirus used to make BREYANZI have limited , short spans of identical genetic material ( RNA ). Therefore , some commercial HIV nucleic acid tests may yield false-positive results in patients who have received BREYANZI .
USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary
There are no available data with BREYANZI use in pregnant women . No animal reproductive and developmental toxicity studies have been conducted with BREYANZI to assess whether it can cause fetal harm when administered to a pregnant woman .
It is not known if BREYANZI has the potential to be transferred to the fetus . Based on the mechanism of action , if the transduced cells cross the placenta , they may cause fetal toxicity , including B-cell lymphocytopenia and hypogammaglobulinemia . Therefore , BREYANZI is not recommended for women who are pregnant , and pregnancy after BREYANZI infusion should be discussed with the treating physician .
In the U . S . general population , the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 % to 4 % and 15 % to 20 %, respectively .
Lactation Risk Summary
There is no information regarding the presence of BREYANZI ( lisocabtagene maraleucel ) in human milk , the effect on the breastfed infant , and the effects on milk production . The developmental and health benefits of breastfeeding should be considered along with the mother ’ s clinical need for BREYANZI and any potential adverse effects on the breastfed infant from BREYANZI or from the underlying maternal condition .
Females and Males of Reproductive Potential Pregnancy Testing
Pregnancy status of females with reproductive potential should be verified . Sexually active females of reproductive potential should have a pregnancy test prior to starting treatment with BREYANZI .
Contraception
See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive lymphodepleting chemotherapy .
There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with BREYANZI .
Infertility There are no data on the effects of BREYANZI on fertility .
Pediatric Use The safety and efficacy of BREYANZI have not been established in pediatric patients .
Geriatric Use
In clinical trials of BREYANZI , 111 ( 41 %) of the 268 patients in TRANSCEND were 65 years of age or older , and 27 ( 10 %) were 75 years of age or older . No clinically important differences in safety or effectiveness of BREYANZI were observed between these patients and younger patients .
PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ).
Ensure that patients understand the risk ( 11 %) of manufacturing failure . In case of a manufacturing failure , a second manufacturing of BREYANZI may be attempted . While the patient awaits the product , additional bridging therapy ( not the lymphodepletion ) may be necessary . This bridging therapy may be associated with adverse events during the pre-infusion period , which could delay or prevent the administration of BREYANZI .
Prior to infusion , advise patients of the following risks :
• Cytokine Release Syndrome ( CRS ) – Signs and symptoms of CRS ( fever , chills , hypotension , tachycardia , hypoxia , and fatigue ). Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time [ see Warnings and Precautions and Adverse Reactions ].
• Neurologic Toxicities – Signs or symptoms associated with neurologic events including encephalopathy , confusion , decreased consciousness , speech disorders , tremor , and seizures . Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time [ see Warnings and Precautions and Adverse Reactions ].
• Serious Infections – Signs or symptoms associated with infection [ see Warnings and Precautions and Adverse Reactions ].
• Prolonged Cytopenias – Signs or symptoms associated with bone marrow suppression including neutropenia , anemia , thrombocytopenia , or febrile neutropenia [ see Warnings and Precautions and Adverse Reactions ].
Advise patients of the need to :
• Contact Bristol-Myers Squibb at 1-888-805-4555 if they are diagnosed with a secondary malignancy [ see Warnings and Precautions ].
• Refrain from driving or operating heavy or potentially dangerous machines until at least 8 weeks after BREYANZI administration [ see Warnings and Precautions ].
REFERENCES
1 . Lee DW , Gardner R , Porter DL , et al . Current concepts in the diagnosis and management of cytokine release syndrome . Blood 2014 ; 124:188-195 .
Manufactured by Juno Therapeutics Inc ., a Bristol-Myers Squibb Company , Bothell , WA 98021
BREYANZI ® is a trademark of Juno Therapeutics , Inc ., a Bristol-Myers Squibb Company .
Pat . https :// www . bms . com / patient-and-caregivers / our-medicines . html © 2021 Juno Therapeutics , Inc ., a Bristol-Myers Squibb Company . All rights reserved . BREPI . 001 / MG . 001
Issued : 02 / 2021 2009-US-2100004 02 / 21