Breyanzi kit Kit Uses, Dosage & Side Effects

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These highlights do not include all the information needed to use BREYANZI safely and effectively. See full prescribing information for BREYANZI. BREYANZI® (lisocabtagene maraleucel) suspension for intravenous infusion Initial U.…

Active ingredients

Lisocabtagene maraleucel · 50000000 1 / 5 mL

Manufacturer

Juno Therapeutics, Inc.

Drug classChimeric antigen receptor (CAR) T-cell therapies

Strength50000000 1 / 5 mL

Dosage formKIT

Registration number73153-900-01

Uses and indications

BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: • adult patients with large B-cell lymphoma (LBCL), 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, who have: • refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or

• refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or

• relapsed or refractory disease after 2 or more lines of systemic therapy. (1.1)

Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma. (1, 14)

• adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. 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). (1.2)

• adult patients with relapsed or refractory follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy. (1.3)

• 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. (1.4)

• adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least 2 prior lines of systemic therapy. (1.5) 1.1 Large B-cell Lymphoma (LBCL)

BREYANZI is indicated for the treatment of adult patients with large B-cell lymphoma (LBCL), 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 who have: • refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or

• relapsed or refractory disease after 2 or more lines of systemic therapy.

Limitations of Use

: BREYANZI is not indicated for the treatment of patients with primary central nervous system (CNS) lymphoma

[see Clinical Studies (14.1)]. 1.2 Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

BREYANZI is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy including, a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor.

This indication is approved under accelerated approval based on response rate and duration of response [see Clinical Studies (14.2)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). 1.3 Follicular Lymphoma (FL)

BREYANZI is 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. 1.4 Mantle Cell Lymphoma (MCL)

BREYANZI is 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. 1.5 Marginal Zone Lymphoma (MZL)

BREYANZI is indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least 2 prior lines of systemic therapy.

Contraindications

None.

Side effects

Cytokine Release Syndrome Identify cytokine release syndrome (CRS) based on clinical presentation [see Warnings and Precautions (5.1)]. Evaluate for and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, manage according to the recommendations in Table…

Cytokine Release Syndrome

Identify cytokine release syndrome (CRS) based on clinical presentation [see Warnings and Precautions (5.1)]. Evaluate for and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, manage according to the recommendations in Table 2.

Physicians may also consider management per current practice guidelines.

Patients who experience Grade 2 or higher CRS (e.g., hypotension not responsive to fluids, or hypoxia requiring supplemental oxygenation) should be monitored with continuous cardiac telemetry and pulse oximetry. For patients experiencing severe CRS, consider performing an echocardiogram to assess cardiac function. For severe or life-threatening CRS, consider intensive-care supportive therapy.

If concurrent neurologic toxicity is suspected during CRS, administer: • Corticosteroids according to the more aggressive intervention based on the CRS and neurologic toxicity grades in Tables 2 and 3

• Tocilizumab according to the CRS grade in Table 2

• Antiseizure medication according to the neurologic toxicity in Table 3

Table 2: CRS Grading and Management Guidance

a Lee criteria for grading CRS (Lee et al, 2014).

b If corticosteroids are initiated, continue corticosteroids for at least 3 doses or until complete resolution of symptoms, and consider corticosteroid taper.

CRS Gradea

Tocilizumab

Corticosteroidsb

Grade 1

Fever

If less than 72 hours after infusion, consider tocilizumab 8 mg/kg IV over 1 hour (not to exceed 800 mg).

If 72 hours or more after infusion, treat symptomatically.

If less than 72 hours after infusion, consider dexamethasone 10 mg IV every 24 hours.

If 72 hours or more after infusion, treat symptomatically.

Grade 2

Symptoms require and respond to moderate intervention.

Oxygen requirement less than 40% FiO2, or hypotension responsive to fluids or low dose of one vasopressor, or Grade 2 organ toxicity.

Administer tocilizumab 8 mg/kg IV over 1 hour (not to exceed 800 mg).

Repeat tocilizumab every 8 hours as needed if not responsive to intravenous fluids or increasing supplemental oxygen.

Limit to a maximum of 3 doses in a 24-hour period; maximum total of 4 doses.

If less than 72 hours after infusion, administer dexamethasone 10 mg IV every 12‑24 hours.

If 72 hours or more after infusion, consider dexamethasone 10 mg IV every 12‑24 hours.

If no improvement within 24 hours or rapid progression, repeat tocilizumab and escalate dose and frequency of dexamethasone (10‑20 mg IV every 6 to 12 hours).

If no improvement or continued rapid progression, maximize dexamethasone, switch to high-dose methylprednisolone 2 mg/kg if needed. After 2 doses of tocilizumab, consider alternative immunosuppressants. Do not exceed 3 doses tocilizumab in 24 hours, or 4 doses in total.

Grade 3

Symptoms require and respond to aggressive intervention.

Oxygen requirement greater than or equal to 40% FiO2, or hypotension requiring high-dose or multiple vasopressors, or Grade 3 organ toxicity, or Grade 4 transaminitis.

Per Grade 2.

Administer dexamethasone 10 mg IV every 12 hours.

If no improvement within 24 hours or rapid progression of CRS, repeat tocilizumab and escalate dose and frequency of dexamethasone (10-20 mg IV every 6 to 12 hours).

Grade 4

Life-threatening symptoms.

Requirements for ventilator support or continuous veno‑venous hemodialysis (CVVHD) or Grade 4 organ toxicity (excluding transaminitis).

Per Grade 2.

Administer dexamethasone 20 mg IV every 6 hours.

If no improvement within 24 hours or rapid progression of CRS, escalate tocilizumab and corticosteroid use. If no improvement or continued rapid progression, maximize dexamethasone, switch to high-dose methylprednisolone 2 mg/kg if needed. After 2 doses of tocilizumab, consider alternative immunosuppressants. Do not exceed 3 doses tocilizumab in 24 hours, or 4 doses in total. Neurologic Toxicity

Monitor patients for signs and symptoms of neurologic toxicities (Table 3). Rule out other causes of neurologic symptoms. Provide intensive care supportive therapy for severe or life-threatening neurologic toxicities. If neurologic toxicity is suspected, manage according to the recommendations in Table 3.

Physicians may also consider management per current practice guidelines.

If concurrent CRS is suspected during neurologic toxicity, administer: • Corticosteroids according to the more aggressive intervention based on the CRS and neurologic toxicity grades in Tables 2 and 3

• Tocilizumab according to the CRS grade in Table 2

• Antiseizure medication according to the neurologic toxicity in Table 3

Table 3: Neurologic Toxicity (NT) Grading and Management Guidance

NT Gradea

Corticosteroids and Antiseizure Medication

a NCI CTCAE criteria for grading neurologic toxicities, version

4.03.

Grade 1

Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis. If 72 hours or more after infusion, observe. If less than 72 hours after infusion, consider dexamethasone 10 mg IV every 12 to 24 hours for 2 to 3 days.

Grade 2

Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis. Dexamethasone 10 mg IV every 12 hours for 2-3 days, or longer for persistent symptoms. Consider taper for a total steroid exposure of greater than 3 days. If no improvement after 24 hours or worsening of neurologic toxicity, increase the dose and/or frequency of dexamethasone up to a maximum of 20 mg IV every 6 hours. If no improvement after another 24 hours, rapidly progressing symptoms, or life-threatening complications arise, give methylprednisolone (2 mg/kg loading dose, followed by 2 mg/kg divided 4 times a day; taper within 7 days).

Grade 3

Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis. Dexamethasone 10 to 20 mg IV every 8 to 12 hours. Steroids are not recommended for isolated Grade 3 headaches. If no improvement after 24 hours or worsening of neurologic toxicity, escalate to methylprednisolone (dose and frequency as per Grade 2). If cerebral edema is suspected, consider hyperventilation and hyperosmolar therapy. Give high-dose methylprednisolone (1-2 g, repeat every 24 hours if needed; taper as clinically indicated) and cyclophosphamide 1.5 g/m2.

Grade 4

Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis. Dexamethasone 20 mg IV every 6 hours. If no improvement after 24 hours or worsening of neurologic toxicity, escalate to methylprednisolone (dose and frequency as per Grade 2). If cerebral edema is suspected, consider hyperventilation and hyperosmolar therapy. Give high-dose methylprednisolone (1-2 g, repeat every 24 hours if needed; taper as clinically indicated), and cyclophosphamide 1.5 g/m2.

The most common adverse reactions (incidence ≥ 30%) in: • LBCL are fever, CRS, fatigue, musculoskeletal pain, and nausea. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decrease, neutrophil count decrease, platelet count decrease, and hemoglobin decrease. (6.1)

• CLL/SLL are CRS, encephalopathy, fatigue, musculoskeletal pain, nausea, edema and diarrhea. The most common Grade 3-4 laboratory abnormalities include neutrophil count decrease, white blood cell decrease, hemoglobin decrease, platelet count decrease, and lymphocyte count decrease. (6.1)

• FL are CRS. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decreased, neutrophil count decreased, and white blood cell decreased. (6.1)

• MCL are CRS, 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. (6.1)

• MZL are CRS. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decreased, neutrophil count decreased, and white blood cell decreased. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact

Bristol-Myers Squibb at 1-800-721-5072

or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety data described in the WARNINGS and PRECAUTIONS and in this section reflects exposure to a single dose of BREYANZI in 769 patients in five clinical studies as described below.

Study 1 (JCAR017-BCM-003; Relapsed or Refractory LBCL After One Line of Therapy)

Study 1 was a randomized, open-label, multicenter study, in which patients with primary refractory LBCL or relapse within 1 year of first-line chemoimmunotherapy received BREYANZI (N=89) or standard therapy (N=91) [see Clinical Studies (14.1)]. Patients had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous HSCT. The trial excluded patients who were ineligible for transplant or who had age > 75 years, Eastern Cooperative Oncology Group (ECOG) performance status >1, history of central nervous system (CNS) disorders (such as seizures or stroke), uncontrolled infection, CrCl < 45 mL/min, alanine aminotransferase (ALT) > 5 times the upper limit of normal (ULN), left ventricular ejection fraction (LVEF) < 40%, or absolute neutrophil count (ANC) < 1.0 × 109 cells/L or platelets < 50 × 109 cells/L in the absence of bone marrow involvement.

The planned dose of BREYANZI was 100 × 106 CAR-positive viable T cells. The median age of the BREYANZI-treated population was 59 years (range: 20 to 74 years); 47% were male; 58% were White, 11% were Asian, and 5% were Black.

Serious adverse reactions occurred in 38% of patients. The most common nonlaboratory serious adverse reactions (> 2%) were CRS, sepsis, fever, febrile neutropenia, headache, aphasia, COVID-19 infection, and pulmonary embolism.

Table 4 presents selected nonlaboratory adverse reactions in patients treated with BREYANZI, and Table 5 describes selected new or worsening Grade 3 or 4 laboratory abnormalities.

The most common nonlaboratory adverse reactions (≥ 20%) were fever, CRS, musculoskeletal pain, headache, fatigue, nausea, constipation, and dizziness.

Table 4: Adverse Reactions in ≥ 10% of Patients with Relapsed or Refractory LBCL Treated with BREYANZI in Study 1 (N=89)

* Represents multiple related terms.

a Dizziness includes dizziness, dizziness postural, syncope, vertigo.

b Motor dysfunction includes fine motor skill dysfunction, muscle spasms, muscular weakness.

c Tremor includes resting tremor, tremor, essential tremor.

d Hemorrhage includes conjunctival hemorrhage, cystitis hemorrhagic, epistaxis, gastrointestinal hemorrhage, hematoma, hematuria, retinal hemorrhage, vaginal hemorrhage.

Adverse Reaction

Any Grade (%)

Grade 3 or Higher (%)

Blood and lymphatic system disorders

Febrile neutropenia

Cardiac disorders

Tachycardia*

1.1

Gastrointestinal disorders

Nausea

Constipation

2.2

Diarrhea

Abdominal pain*

2.2

Vomiting

General disorders and administration site conditions

Fever

3.4

Fatigue*

1.1

Edema*

Immune system disorders

Cytokine release syndrome

1.1

Infections and infestations

Bacterial infectious disorders*

Infections with pathogen unspecified*

Sepsis*

Metabolism and nutrition disorders

Decreased appetite

Musculoskeletal and connective tissue disorders

Musculoskeletal pain*

3.4

Nervous system disorders

Headache*

Dizzinessa

1.1

Motor dysfunctionb

3.4

Tremorc

1.1

Psychiatric disorders

Insomnia*

Respiratory, thoracic, and mediastinal disorders

Cough*

Skin and subcutaneous tissue disorders

Rash*

1.1

Vascular disorders

Hypotension*

2.2

Hemorrhaged

Other clinically important adverse reactions in < 10% of patients treated with BREYANZI included the following: • Immune system disorders: Hemophagocytic lymphohistiocytosis (1.1%)

• Infections and infestations: Viral infection (9%), fungal infection (4.5%), pneumonia (2.2%)

• Nervous system disorders: Encephalopathy (8%), aphasia (4.5%), peripheral neuropathy (4.5%), ataxia (3.4%), paresis (1.1%)

• Psychiatric disorders: Delirium (2.2%)

• Renal and urinary disorders: Renal failure (3.4%)

• Respiratory, thoracic, and mediastinal disorders: Dyspnea (8%)

• Vascular disorders: Thrombosis (8%), hypertension (7%)

Table 5: Grade 3 or 4 Laboratory Abnormalities Occurring in ≥ 10% of Patients with Relapsed or Refractory LBCL Treated with BREYANZI in Study 1

a Baseline lab values were assessed prior to lymphodepleting chemotherapy.

b Based on 88 evaluable patients, defined as those with both a baseline grade and at least one post-baseline grade for the particular lab.

Laboratory Abnormalitya

Grade 3 or 4 (%)b

Lymphocyte count decreased

Neutrophil count decreased

Platelet count decreased

Hemoglobin decreased

Grade 4 laboratory abnormalities in ≥ 10% of patients were lymphocyte decrease (64%), neutrophil decrease (66%), and platelet decrease (34%).

Study 2 (017006; Relapsed or Refractory LBCL After One Line of Therapy)

Study 2 was a single-arm open-label study in transplant-ineligible patients with R/R LBCL after one line of chemoimmunotherapy [see Clinical Studies (14.1)]. The study enrolled patients who were ineligible for high-dose therapy and autologous HSCT due to organ function or age, but who had adequate organ function for CAR-T cell therapy. Patients with a history of relevant CNS disorders (such as seizures or stroke), ECOG performance status > 2, or uncontrolled infection were ineligible. The trial required LVEF ≥ 40%, adequate oxygen saturation on room air with ≤ Grade 1 dyspnea, AST, and ALT ≤ 5 x ULN, total bilirubin < 2.0 mg/dL, creatinine clearance > 30 mL/min, and adequate bone marrow function to receive lymphodepleting chemotherapy. The planned dose of BREYANZI was 100 × 106 CAR-positive viable T cells.

The median age was 74 years (range: 53 to 84 years), 90% were age ≥ 65 years, 61% were male. The ECOG performance status was 0 or 1 in 74% of patients and 2 in 26% of patients; 25% had CrCl < 60 ml/min; 20% had a baseline ANC < 1000/μL.

Serious adverse reactions occurred in 33% of patients. The most common nonlaboratory, serious adverse reactions (> 2%) were CRS, confusional state, gastrointestinal hemorrhage, muscular weakness, musculoskeletal pain, pulmonary embolism, and sepsis.

Table 6 presents selected nonlaboratory adverse reactions, and Table 7 describes selected new or worsening Grade 3 or 4 laboratory abnormalities.

The most common nonlaboratory adverse reactions (≥ 20%) were fatigue, CRS, fever, nausea, encephalopathy, hypotension, musculoskeletal pain, and edema.

Table 6: Adverse Reactions in ≥ 10% of Patients with Relapsed or Refractory LBCL Treated with BREYANZI in Study 2 (N=61)

* Represents multiple related terms.

a Encephalopathy includes amnesia, apraxia, cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, dyscalculia, encephalopathy, lethargy, memory impairment, mental status changes, somnolence.

b Dizziness includes dizziness, dizziness postural, syncope, vertigo.

c Tremor includes resting tremor, tremor.

Adverse Reaction

Any Grade (%)

Grade 3 or Higher (%)

Cardiac disorders

Tachycardia*

Gastrointestinal disorders

Nausea

1.6

Diarrhea

Constipation

General disorders and administration site conditions

Fatigue*

1.6

Fever

1.6

Edema*

Immune system disorders

Cytokine release syndrome

1.6

Infections and infestations

Infections with pathogen unspecified*

4.9

Upper respiratory tract infection*

Bacterial infectious disorders*

3.3

Metabolism and nutrition disorders

Decreased appetite

1.6

Musculoskeletal and connective tissue disorders

Musculoskeletal pain*

4.9

Nervous system disorders

Encephalopathya

4.9

Dizzinessb

1.6

Tremorc

Headache

1.6

Psychiatric disorders

Insomnia

Respiratory, thoracic, and mediastinal disorders

Cough*

Dyspnea*

4.9

Vascular disorders

Hypotension*

1.6

Hypertension

4.9

Other clinically important adverse reactions in < 10% of patients included the following: • Blood and lymphatic system disorders: Febrile neutropenia (1.6%)

• Eye disorders: Vision blurred (3.3%)

• Gastrointestinal disorders: Vomiting (8%), abdominal pain (7%), gastrointestinal hemorrhage (4.9%)

• Infections and infestations: Fungal infection (4.9%), sepsis (3.3%), viral infection (3.3%)

• Nervous system disorders: Motor dysfunction (7%), aphasia (4.9%), ataxia (4.9%), peripheral neuropathy (4.9%)

• Psychiatric disorders: Delirium (3.3%)

• Renal and urinary disorders: Renal failure (7%)

• Respiratory, thoracic, and mediastinal disorders: Hypoxia (4.9%)

• Skin and subcutaneous tissue disorders: Rash (7%)

• Vascular disorders: Thrombosis (7%)

Table 7: Grade 3 or 4 Laboratory Abnormalities Occurring in ≥ 10% of Patients with Relapsed or Refractory LBCL Treated with BREYANZI in Study 2 (N=61)

a Baseline lab values were assessed prior to lymphodepleting chemotherapy.

Laboratory Abnormalitya

Grade 3 or 4 (%)

Lymphocyte count decreased

Neutrophil count decreased

Hemoglobin decreased

Platelet count decreased

Grade 4 laboratory abnormalities in ≥ 10% of patients were lymphocyte decrease (95%), neutrophil decrease (57%), and platelet decrease (20%).

Study 3 (017001; Relapsed or Refractory LBCL After Two or More Lines of Therapy)

Study 3 was an open-label, single-arm study which evaluated 268 adult patients with R/R LBCL after 2 or more prior lines of therapy received a single dose of CAR-positive viable T cells [see Clinical Studies (14.1)]. Patients with a history of CNS disorders (such as seizures or stroke) or autoimmune disease requiring systemic immunosuppression were ineligible. The median age of the study population was 63 years (range: 18 to 86 years); 65% were male. The ECOG performance status at screening was 0 in 41% of patients, 1 in 58% of patients, and 2 in 1.5% of patients.

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.

Table 8 presents selected nonlaboratory adverse reactions reported in patients treated with BREYANZI, and Table 9 describes selected new or worsening Grade 3 or 4 laboratory abnormalities.

The most common nonlaboratory adverse reactions (≥ 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.

Table 8: Adverse Reactions in ≥ 10% of Patients with Relapsed or Refractory LBCL Treated with BREYANZI in Study 3 (N=268)

* Represents multiple related terms.

a 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.

b Dizziness includes dizziness, presyncope, syncope, vertigo.

c Tremor includes essential tremor, resting tremor, tremor.

d Peripheral neuropathy includes hyperesthesia, hypoesthesia, meralgia paresthetica, neuralgia, neuropathy peripheral, paresthesia, peripheral sensory neuropathy, sciatica, sensory loss.

e Aphasia includes aphasia, disorganized speech, dysarthria, dysphemia, dysphonia, slow speech, speech disorder.

f Motor dysfunction includes eyelid ptosis, motor dysfunction, muscle rigidity, muscle spasms, muscle spasticity, muscle tightness, muscle twitching, muscular weakness, myoclonus, myopathy.

g Delirium includes agitation, delirium, delusion, disorientation, hallucination, hallucination, visual, irritability, restlessness.

h Hemorrhage includes catheter site hemorrhage, conjunctival hemorrhage, epistaxis, hematoma, hematuria, hemorrhage, hemorrhage intracranial, pulmonary hemorrhage, retinal hemorrhage, vaginal hemorrhage.

Adverse Reaction

Any Grade (%)

Grade 3 or Higher (%)

Cardiac disorders

Tachycardia*

Gastrointestinal disorders

Nausea

1.5

Diarrhea

0.4

Constipation

Abdominal pain*

3.0

Vomiting

0.4

General disorders and administration site conditions

Fatigue*

3.4

Edema*

1.1

Fever

Chills

Immune system disorders

Cytokine release syndrome

4.1

Infections and infestations*

Infection with pathogen unspecified*

Bacterial infection*

Upper respiratory tract infection*

0.7

Viral infection

1.5

Metabolism and nutrition disorders

Decreased appetite

2.6

Musculoskeletal and connective tissue disorders

Musculoskeletal pain*

2.2

Nervous system disorders

Headache*

1.1

Encephalopathya

Dizzinessb

2.6

Tremorc

Peripheral neuropathyd

Aphasiae

2.2

Motor dysfunctionf

1.1

Psychiatric disorders

Insomnia*

0.4

Anxiety*

Deliriumg

2.2

Renal and urinary disorders

Renal failure*

3.0

Respiratory, thoracic, and mediastinal disorders

Cough*

Dyspnea*

2.6

Skin and subcutaneous tissue disorders

Rash*

0.4

Vascular disorders

Hypotension*

3.4

Hypertension

4.5

Hemorrhageh

1.5

Other clinically important adverse reactions in < 10% of patients included the following: • Cardiac disorders: Arrhythmia (6%), cardiomyopathy (1.5%)

• Gastrointestinal disorders: Gastrointestinal hemorrhage (4.1%)

• Infections and infestations: Pneumonia (8%), fungal infection (8%), sepsis (4.5%), urinary tract infection (4.1%)

• Metabolism and nutrition disorders: Tumor lysis syndrome (0.7%)

• Nervous system disorders: Ataxia or gait disturbance (7%), visual disturbance (5%), paresis (2.6%), cerebrovascular events (1.9%), seizure (1.1%), brain edema (0.4%)

• Procedural complications: Infusion-related reaction (1.9%)

• Respiratory, thoracic, and mediastinal disorders: Pleural effusion (7%), hypoxia (6%)

• Vascular disorder: Thrombosis (7%)

Table 9: Grade 3 or 4 Laboratory Abnormalities Occurring in ≥ 10% of Patients with Relapsed or Refractory LBCL Treated with BREYANZI in Study 3

a Baseline lab values were assessed prior to lymphodepleting chemotherapy.

b The denominator varied from 239 to 268, based on the number of patients with a baseline value and at least one post-treatment value for the particular lab.

Laboratory Abnormalitya

Grade 3 or 4 (%)b

Lymphocyte count decreased

Neutrophil count decreased

Platelet count decreased

Hemoglobin decreased

Phosphate decreased

Fibrinogen decreased

Study 4 (017004; Relapsed or Refractory CLL/SLL)

Study 4 was an open-label, single-arm study which evaluated 89 adult patients with R/R CLL/SLL who had received at least 2 prior lines of therapy including a BTK inhibitor and a BCL-2 inhibitor before receiving a single dose of CAR-positive viable T cells [see Clinical Studies (14.2)]. Patients with a history of CNS disorders (such as seizures or stroke) or autoimmune disease requiring systemic immunosuppression, Richter’s transformation, ECOG performance status > 1 were ineligible. The trial required LVEF ≥ 40%, adequate oxygen saturation on room air with ≤ Grade 1 dyspnea, ALT ≤ 5 x ULN, total bilirubin < 2.0 mg/dL, creatinine clearance > 30 mL/min, and adequate bone marrow function to receive lymphodepleting chemotherapy.

The median age of the study population was 66 years (range: 49 to 82 years); 69% were male, 84% were White, 3% were Black, 1% were Asian. Two percent were Hispanic, and 89% were non-Hispanic. The ECOG performance status at screening was 0 in 40% of patients, and 1 in 60% of patients.

Serious adverse reactions occurred in 60% of patients. The most common nonlaboratory serious adverse reactions (> 2%) were CRS, encephalopathy, febrile neutropenia, pneumonia, hemorrhage, fever, renal failure, aphasia, abdominal pain, delirium, tumor lysis syndrome, upper respiratory tract infection, and hemophagocytic lymphohistiocytosis [IEC-HS]. Fatal adverse reactions occurred in 1.1% of patients.

Table 10 presents selected nonlaboratory adverse reactions reported in patients treated with BREYANZI, and Table 11 describes selected new or worsening Grade 3 or 4 laboratory abnormalities.

The most common nonlaboratory adverse reactions (≥ 20%) were CRS, encephalopathy, fatigue, musculoskeletal pain, nausea, edema, diarrhea, dyspnea, headache, fever, decreased appetite, constipation, tremor, dizziness, Infection with pathogen unspecified, rash, tachycardia, cough, and delirium.

Table 10: Adverse Reactions in ≥ 10% of Patients with Relapsed or Refractory CLL/SLL Treated with BREYANZI in Study 4 (N=89)

* Represents multiple related terms.

a Encephalopathy includes cognitive disorder, confusional state, disturbance in attention, encephalopathy, lethargy, memory impairment, mental status changes, somnolence.

b Dizziness includes dizziness, presyncope, syncope, vertigo.

c Motor dysfunction includes asterixis, muscle spasms, muscular weakness, myoclonus.

dPeripheral neuropathy includes hyperesthesia, hypoesthesia, neuralgia, neuropathy peripheral, paresthesia, peripheral sensory neuropathy.

e Delirium includes agitation, delirium, hallucination, hallucination visual, intensive care unit delirium, irritability, restlessness.

fHemorrhage includes epistaxis, hemorrhage intracranial, hematoma, hematuria, hemorrhoidal hemorrhage, intraventricular hemorrhage, lower gastrointestinal hemorrhage, traumatic hemothorax.

Adverse Reaction

Any Grade (%)

Grade 3 or Higher (%)

Blood and lymphatic system disorders

Febrile neutropenia

Cardiac disorders

Tachycardia*

Gastrointestinal disorders

Nausea

Diarrhea*

1.1

Constipation

Abdominal pain*

Vomiting

General disorders and administration site conditions

Fatigue*

4.5

Edema*

4.5

Fever*

1.1

Chills

1.1

Immune system disorders

Cytokine release syndrome

Infections and infestations

Infection with pathogen unspecified*

Upper respiratory tract infection*

1.1

Viral infection*

1.1

Metabolism and nutrition disorders

Decreased appetite

4.5

Tumor lysis syndrome

Musculoskeletal and connective tissue disorders

Musculoskeletal pain*

1.1

Nervous system disorders

Encephalopathya

Headache*

1.1

Tremor

2.2

Dizzinessb

1.1

Motor dysfunctionc

2.2

Peripheral neuropathyd

Taste disorder*

Psychiatric disorders

Deliriume

3.4

Insomnia

1.1

Anxiety

1.1

Renal and urinary disorders

Renal failure*

3.4

Respiratory, thoracic, and mediastinal disorders

Dyspnea*

Cough*

Skin and subcutaneous tissue disorders

Rash*

2.2

Vascular disorders

Hypotension*

Hemorrhagef

1.1

Hypertension

4.5

Other clinically important adverse reactions in < 10% of patients included the following: • Cardiac disorders: Chest discomfort (4.5%), Arrhythmia (2.2%).

• Eye disorders: Vision blurred (4.5%).

• Gastrointestinal disorders: Dyspepsia (9%), abdominal distension (7%).

• Immune system disorders: Hemophagocytic lymphohistiocytosis [IEC-HS] (3.4%).

• Infections and infestations: Fungal infection (9%), pneumonia (7%), urinary tract infection (7%), bacterial infectious disorders (4.5%), sepsis (2.2%).

• Injury, poisoning and procedural complications: Infusion related reaction (1.1%).

• Nervous system disorders: Aphasia (8%), Ataxia (3.4%), Paresis (3.4%), Seizure (1.1%).

• Psychiatric disorders: Affective disorder (7%).

• Respiratory, thoracic, and mediastinal disorders: Oral pain (8%), hypoxia (8%).

• Skin and subcutaneous tissue disorders: Ecchymosis (8%), xerosis (7%), pruritus (6%).

• Vascular disorder: Thrombosis (6%).

Table 11: Grade 3 or 4 Laboratory Abnormalities Occurring in ≥ 10% of Patients with Relapsed or Refractory CLL/SLL Treated with BREYANZI in Study 4

a Baseline lab values were assessed prior to lymphodepleting chemotherapy.

b The denominator ranged from 85 to 89 for other measurements, based on the number of patients with a baseline value and at least one post-treatment value for the particular lab.

Laboratory Abnormalitya

Grade 3 or 4 (%)b

Neutrophil count decreased

Lymphocyte count decreased

White blood cell decreased

Platelet count decreased

Hemoglobin decreased

Hypophosphatemia

Hyponatremia

Hypocalcemia

Grade 4 laboratory abnormalities in ≥ 10% of patients were neutrophil count decreased (81%), lymphocyte count decreased (73%), white blood cell decreased (72%), and platelet count decreased (30%).

Study 5 (JCAR017-FOL-001; Relapsed or Refractory FL Cohort)

Study 5 was an open-label, single-arm study which evaluated 107 adult patients with relapsed or refractory FL after two or more prior lines of therapy received a single dose of CAR-positive viable T cells

[see Clinical Studies (14.3)].

Patients with a history of CNS disorders (such as seizures or stroke) and active autoimmune disease requiring immunosuppressive therapy were ineligible. The median age was 62 years (range: 23 to 80 years), 38 % were female, and ECOG performance status was 0 in 61% and 1 in 39% of patients; 56% were White, 3% were Black, 9% were Asian; 5% were Hispanic and 69% were non-Hispanic.

Serious adverse reactions occurred in 26% of patients. The most common nonlaboratory serious adverse reactions (> 2%) were CRS, aphasia, febrile neutropenia, fever, and tremor.

Table 12 presents selected nonlaboratory adverse reactions reported in patients treated with BREYANZI, and Table 13 describes selected new or worsening Grade 3 or 4 laboratory abnormalities.

The most common nonlaboratory adverse reactions (≥ 20%) were CRS, headache, musculoskeletal pain, fatigue, constipation, and fever.

Table 12: Adverse Reactions** in ≥ 10% of Patients with Relapsed or Refractory FL Treated with BREYANZI in Study 5 (N=107)

* Represents multiple related terms.

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

Adverse Reaction

Any Grade (%)

Grade 3 or Higher (%)

Gastrointestinal disorders

Constipation

Diarrhea

General disorders and administration site conditions

Fatigue*

Fever*

Immune system disorders

Cytokine release syndrome

0.9

Infections and infestations

Infection with pathogen unspecified*

4.7

Musculoskeletal and connective tissue disorders

Musculoskeletal pain*

Nervous system disorders

Headache

Tremor

Other clinically important adverse reactions in < 10% of patients included the following: • Blood and lymphatic system disorders: Febrile neutropenia (6%).

• Cardiac disorders: Tachycardia (2.8%).

• Eye disorders: Vision blurred (1.9%).

• Gastrointestinal disorders: Nausea (9%), abdominal pain (4.7%), vomiting (3.7%).

• General disorders and administration site conditions: Edema (4.7%), chills (3.7%).

• Infections and infestations: Upper respiratory tract infection (8%), bacterial infectious disorders (6%), urinary tract infection (4.7%), viral infectious disorders (1.9%), pneumonia (1.9%), sepsis (0.9%).

• Nervous system disorders: Encephalopathy (7%), aphasia (8%), dizziness (4.7%), motor dysfunction (3.7%), ataxia (3.7%), neuropathy peripheral (4.7%).

• Psychiatric disorders: Insomnia (4.7%), delirium (4.7%), anxiety (1.9%).

• Renal and urinary disorders: Acute kidney injury (0.9%).

• Respiratory, thoracic and mediastinal disorders: Cough (7%), dyspnea (1.9%), hypoxia (1.9%).

• Vascular disorders: Hypotension (8%), hypertension (6%), thrombosis (4.7%).

• Skin and subcutaneous tissue disorders: Rash (7%).

Table 13: Grade 3 or 4 Laboratory Abnormalities* Occurring in ≥ 10% of Patients with Relapsed or Refractory FL Treated with BREYANZI in Study 5 (N=107)

*Includes laboratory abnormalities up to 90 days following treatment with BREYANZI.

a Baseline lab values were assessed prior to lymphodepleting chemotherapy.

b Based on the number of patients with a baseline value and at least one post treatment value for the particular lab.

Laboratory Abnormalitya

Grade 3 or 4 (%)b

Lymphocyte count decreased

Neutrophil count decreased

White blood cell decreased

Platelet count decreased

Grade 4 laboratory abnormalities in ≥ 10% of patients were lymphocyte count decreased (78%), neutrophil count decreased (61%), white blood cell decreased (41%), and platelet count decreased (11%).

Study 3 (017001; Relapsed or Refractory MCL Cohort)

Study 3 was an open-label, single-arm study which evaluated 88 adult patients with relapsed or refractory MCL who received a single dose of CAR-positive viable T cells [see Clinical Studies (14.4)]. Patients with a history of CNS disorders (such as seizures or stroke) or autoimmune disease requiring systemic immunosuppression were ineligible. The trial required left ventricular ejection fraction ≥ 40%, adequate oxygen saturation on room air with ≤ Grade 1 dyspnea, ALT ≤ 5 x ULN, total bilirubin < 2.0 mg/dL, creatinine clearance > 30 mL/min, and adequate bone marrow function to receive lymphodepleting chemotherapy. The median age of the study population was 69 years (range: 36 to 86 years); 76% were male, 88% were White, 6% were Asian and 2.3% were Black. Four percent were Hispanic, and 92% were non-Hispanic. The ECOG performance status at screening was 0 in 54% of patients, and 1 in 46% of patients.

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.

Table 14 presents selected nonlaboratory adverse reactions reported in patients treated with BREYANZI, and Table 15 describes selected new or worsening Grade 3 or 4 laboratory abnormalities.

The most common nonlaboratory adverse reactions (≥ 20%) were CRS, fatigue, musculoskeletal pain, encephalopathy, edema, headache, and decreased appetite.

Table 14: Adverse Reactions** in ≥ 10% of Patients with Relapsed or Refractory MCL Treated with BREYANZI in Study 3 (N=88)

* Represents multiple related terms.

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

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

b Dizziness includes dizziness, dizziness postural, syncope, vertigo.

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

d Hemorrhage includes catheter site hemorrhage, epistaxis, hematoma, hematuria, hemorrhage, hemorrhoidal hemorrhage, rectal hemorrhage.

Adverse Reaction

Any Grade (%)

Grade 3 or Higher (%)

Cardiac disorders

Tachycardia*

3.4

Gastrointestinal disorders

Nausea

2.3

Diarrhea

Abdominal pain*

3.4

Constipation

General disorders and administration site conditions

Fatigue*

2.3

Edema*

1.1

Fever*

Chills

Immune system disorders

Cytokine release syndrome

1.1

Infections and infestations

Infection with pathogen unspecified*

Upper respiratory tract infection*

2.3

Metabolism and nutrition disorders

Decreased appetite

4.5

Musculoskeletal and connective tissue disorders

Musculoskeletal pain*

2.3

Nervous system disorders

Encephalopathya

Headache

Dizzinessb

2.3

Motor dysfunctionc

Tremor

Psychiatric disorders

Insomnia*

Anxiety

1.1

Renal and urinary disorders

Renal failure*

Respiratory, thoracic, and mediastinal disorders

Dyspnea*

Cough

Skin and subcutaneous tissue disorders

Rash*

1.1

Vascular disorders

Hypotension*

Hemorrhaged

Hypertension

3.4

Other clinically important adverse reactions in < 10% of patients included the following: • Blood and lymphatic system disorders: Febrile neutropenia (6%).

• Cardiac disorders: Arrhythmia (2.3%).

• Eye disorders: Vision blurred (3.4%).

• Gastrointestinal disorders: Vomiting (6%).

• Infections and infestations: Bacterial infection (9%), viral infection (9%), fungal infection (8%), urinary tract infection (6%), sepsis (3.4%), pneumonia (2.3%).

• Injury, poisoning and procedural complications: Infusion related reaction (4.5%).

• Metabolism and nutrition disorders: Tumor lysis syndrome (2.3%).

• Nervous system disorders: Neuropathy peripheral (9%), aphasia (8%), ataxia (4.5%), cerebral infarction (1.1%), seizure (1.1%).

• Psychiatric disorders: Delirium (7%).

• Respiratory, thoracic, and mediastinal disorders: Hypoxia (3.4%).

• Vascular disorder: Thrombosis (4.5%).

Table 15: Grade 3 or 4 Laboratory Abnormalities* Occurring in ≥ 10% of Patients with Relapsed or Refractory MCL Treated with BREYANZI in Study 3

*Includes lab abnormalities up to 90 days following treatment with BREYANZI.

a Baseline lab values were assessed prior to lymphodepleting chemotherapy.

b The denominator ranged from 87 to 88 for laboratory measurements, based on the number of patients with a baseline value and at least one post-treatment value for the particular lab.

Laboratory Abnormalitya

Grade 3 or 4 (%)b

Lymphocyte count decreased

Neutrophil count decreased

White blood cell decreased

Platelet count decreased

Hemoglobin decreased

Uric acid increased

Sodium decreased

Grade 4 laboratory abnormalities in ≥ 10% of patients were lymphocyte count decreased (84%), neutrophil count decreased (52%), white blood cell decreased (52%), and platelet count decreased (22%).

Study 5 (JCAR017-FOL-001; Relapsed or Refractory MZL Cohort)

Study 5 was a an open-label, single-arm study which evaluated 67 adult patients with relapsed or refractory MZL after two or more prior lines of therapy or relapsed after hematopoietic stem cell transplant (HSCT) received a single dose of CAR-positive viable T cells [see Clinical Studies (14.5)]. Patients who had previously received CD19-directed therapy had to have biopsy proven CD19 positive lymphoma [see Clinical Studies (14)]. Patients with a history of CNS disorders (such as seizures or stroke) and active autoimmune disease requiring immunosuppressive therapy were ineligible. The median age was 62 years (range: 37 to 81 years), 58% were male, ECOG performance status was 0 in 55% and 1 in 45% of patients; 57% were White, 6% were Asian, 2% were Black; race was not reported in 36% of patients; and 2% were Hispanic.

Serious adverse reactions occurred in 39% of patients. The most common nonlaboratory serious adverse reactions (> 2%) were CRS, encephalopathy, aphasia, sepsis, tremor, delirium, dizziness, infusion related hypersensitivity reaction, and transient ischemic attack. Fatal adverse reactions occurred in 3% of patients.

Table 16 presents nonlaboratory adverse reactions reported in ≥ 10% of patients treated with BREYANZI, and Table 17 describes selected new or worsening Grade 3 or 4 laboratory abnormalities.

The most common nonlaboratory adverse reactions (≥ 20%) were CRS, diarrhea, fatigue, musculoskeletal pain, and headache.

Table 16: Adverse Reactions** in ≥ 10% of Patients with Relapsed or Refractory MZL Treated with BREYANZI in Study 5 (N=67)

* Represents multiple related terms.

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

a Encephalopathy includes brain fog, cognitive disorder, confusional state, disturbance in attention, dyscalculia, dysgraphia, memory impairment, somnolence.

b Delirium includes delirium, disorientation, hallucination, irritability, restlessness.

Adverse Reaction

Any Grade (%)

Grade 3 or Higher (%)

Gastrointestinal disorders

Diarrhea

1.5

Nausea

1.5

Abdominal pain*

General disorders and administration site conditions

Fatigue*

Edema*

Fever*

Immune system disorders

Cytokine release syndrome

4.5

Infections and infestations

Infection with pathogen unspecified*

Metabolism and nutrition disorders

Decreased appetite

Musculoskeletal and connective tissue disorders

Musculoskeletal pain*

Nervous system disorders

Headache

1.5

Tremor

Encephalopathya

1.5

Dizziness

Aphasia

Psychiatric disorders

Deliriumb

Renal and urinary disorders

Renal failure*

1.5

Vascular disorders

Hypotension

Other clinically important adverse reactions in < 10% of patients included the following: • Blood and lymphatic system disorders: Febrile neutropenia (3%).

• Cardiac disorders: Tachycardia (7.5%).

• Gastrointestinal disorders: Vomiting (9%), constipation (3%), dyspepsia (3%).

• General disorders and administration site conditions: Chills (7.5%), infusion related hypersensitivity reactions (3%).

• Immune system disorders: Hemophagocytic lymphohistiocytosis (4.5%).

• Infections and infestations: Bacterial infections (6%), viral infections (6%), fungal infections (3%).

• Metabolism and nutrition disorders: Tumor lysis syndrome (1.5%).

• Nervous system disorders: Motor dysfunction (4.5%), ataxia (3%), neuropathy peripheral (3%), transient ischaemic attack (3.0%).

• Psychiatric disorders: Insomnia (9%), affective disorder (7.5%).

• Respiratory, thoracic and mediastinal disorders: Dyspnea (6%), cough (4.5%), hypoxia (4.5%).

• Skin and subcutaneous tissue disorders: Rash (4.5%).

• Vascular disorders: Hemorrhage (9%), hypertension (6%), thrombosis (6%).

Table 17: Grade 3 or 4 Laboratory Abnormalities* Occurring in ≥ 10% of Patients with Relapsed or Refractory MZL Treated with BREYANZI in Study 5 (N=67)

* Includes laboratory abnormalities up to 90 days following treatment with BREYANZI.

a Baseline lab values were assessed prior to lymphodepleting chemotherapy.

b Based on the number of patients with a baseline value and at least one post treatment value for the particular lab.

Laboratory Abnormalitya

Grade 3 or 4 (%)b

Lymphocyte count decreased

Neutrophil count decreased

White blood cell decreased

Platelet count decreased

Hemoglobin decreased

Fibrinogen decreased

Grade 4 laboratory abnormalities in ≥ 10% of patients were lymphocyte count decreased (85%), neutrophil count decreased (64%), white blood cell decreased (49%), and platelet count decreased (19%). 6.2 Postmarketing Experience

Because adverse events to marketed products are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure.

The following adverse events have been identified during postmarketing use of BREYANZI.

Nervous System Disorder: Immune effector cell-associated neurotoxicity syndrome (ICANS).

Neoplasms: T cell malignancies

Eye disorders: Blindness

Precautions

• Hypersensitivity Reactions: Monitor for hypersensitivity reactions during infusion. (5.3) • Serious Infections: Monitor patients for signs and symptoms of infection; treat appropriately. (5.4) • Prolonged Cytopenias: Patients may exhibit Grade 3 or higher cytopenias for…

• Hypersensitivity Reactions: Monitor for hypersensitivity reactions during infusion. (5.3)

• Serious Infections: Monitor patients for signs and symptoms of infection; treat appropriately. (5.4)

• Prolonged Cytopenias: Patients may exhibit Grade 3 or higher cytopenias for several weeks following BREYANZI infusion. Monitor complete blood counts. (5.5)

• Hypogammaglobulinemia: Monitor and consider immunoglobulin replacement therapy. (5.6)

• 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. In the event that a secondary malignancy occurs after treatment with BREYANZI, contact Bristol-Myers Squibb at 1-888-805-4555. (5.7) 5.1 Cytokine Release Syndrome

Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI.

In clinical trials of BREYANZI, which included a total of 769 patients with non-Hodgkin lymphoma (NHL) exposed to BREYANZI, CRS occurred in 56% of patients, including ≥ Grade 3 CRS (Lee grading system1) in 3.4% of patients. The median time to onset was 5 days (range: 1 to 63 days). CRS resolved in 99% 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%) included fever, hypotension, chills, tachycardia, 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)

[see Adverse Reactions (6.1)].

Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI.

Monitor patients daily for at least 7 days following BREYANZI infusion for signs and symptoms of CRS. Continue to monitor patients for signs or symptoms of CRS for at least 2 weeks after infusion. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated [see Dosage and Administration (2.2, 2.3)].

Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time

[see Patient Counseling Information (17)]. 5.2 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 32% 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 7.5 days (range: 1 to 119 days). Of patients developing neurotoxicity, 83% also developed CRS.

The most common neurologic toxicities (≥ 5%) included encephalopathy, tremor, aphasia, delirium, and headache.

Monitor patients daily for at least 7 days following BREYANZI infusion for signs and symptoms of neurologic toxicities and assess for other causes of neurological symptoms. Continue to monitor patients for signs or symptoms of neurologic toxicities for at least 2 weeks after infusion and treat promptly. Manage neurologic toxicity with supportive care and/or corticosteroid as needed [see Dosage and Administration (2.2, 2.3)]. Advise patients to avoid driving for at least 2 weeks following infusion.

Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time [see Patient Counseling Information (17)]. 5.3 Hypersensitivity Reactions

Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO). 5.4 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 occurred in 12% of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7%, bacterial infections in 3.5%, viral infections in 2%, and fungal infections in 0.7% of patients. One patient with FL, 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. One patient with MCL, who received three 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. 5.5 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. 5.6 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 9% 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. 5.7 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 [see Boxed Warning, Adverse Reactions (6.2), Patient Counseling Information (17)]. 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. 5.8 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. Seven out of 769 (0.9%) patients with R/R NHL exposed to BREYANZI developed IEC-HS (1 LBCL; 3 CLL/SLL; 3 MZL). Time to onset of IEC-HS ranged from 7 to 32 days. Of the 7 patients, 3 patients developed IEC-HS with overlapping occurrence of CRS and neurotoxicity, 2 patients developed IEC-HS with overlapping occurrence of neurotoxicity, and 1 patient developed IEC-HS with overlapping occurrence of CRS. IEC-HS was fatal in 2 of 7 patients. One patient had fatal IEC-HS and one had ongoing IEC-HS at time of death.

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.

Dosage

For autologous use only. For intravenous use only. • Do NOT use a leukodepleting filter. (2.2) • Administer a lymphodepleting regimen of fludarabine and cyclophosphamide before infusion of BREYANZI. (2.2) • Verify the patient’s identity prior to infusion. (2.2) • Premedicate with acetaminophen and an H1 antihistamine. (2.2) • Confirm availability of tocilizumab prior to infusion. (2.2, 5.1) • Dosing of BREYANZI is based on the number of chimeric antigen receptor (CAR)-positive viable T cells. (2.1) • For LBCL: • after one line of therapy, the dose is 90 to 110 × 106 CAR-positive viable T cells. (2.1) • after two or more lines of therapy, the dose is 50 to 110 × 106 CAR-positive viable T cells. (2.1) • For CLL/SLL, FL, MCL and MZL: • the dose is 90 to 110 × 106 CAR-positive viable T cells. (2.1) 2.1 Dose For autologous use only. For intravenous use only. See the respective Certificate of Release for Infusion (RFI Certificate) for each component, for the actual cell counts and volumes to be infused [see Dosage and Administration (2.2) and Dosage Forms and Strengths (3)]. A single dose of BREYANZI contains CAR-positive viable T cells (consisting of 1: 1 CAR-positive viable T cells of the CD8 and CD4 components), with each component supplied separately in one to four single-dose vials. See Table 1 for dose range per indication. Table 1: Dose Range Abbreviations: LBCL = large B-cell lymphoma; CLL = chronic lymphocytic leukemia; SLL = small lymphocytic lymphoma; FL = follicular lymphoma; MCL = mantle cell lymphoma; MZL = marginal zone lymphoma. Indication BREYANZI dose range LBCL after two or more lines of therapy (1.1) 50 to 110 × 106 CAR-positive viable T cells LBCL after one line of therapy (1.1) 90 to 110 × 106 CAR-positive viable T cells CLL or SLL (1.2) 90 to 110 × 106 CAR-positive viable T cells FL (1.3) 90 to 110 × 106 CAR-positive viable T cells MCL (1.4) 90 to 110 × 106 CAR-positive viable T cells MZL (1.5) 90 to 110 × 106 CAR-positive viable T cells 2.2 Administration BREYANZI is for autologous use only. The patient’s identity must match the patient identifiers on the BREYANZI cartons, vials, and syringe labels. Do not infuse BREYANZI if the information on the patient-specific labels does not match the intended patient. Preparing the Patient for BREYANZI Confirm the availability of BREYANZI before starting lymphodepleting chemotherapy. Pretreatment Administer the lymphodepleting chemotherapy regimen before infusion of BREYANZI: fludarabine 30 mg/m2/day intravenously (IV), and cyclophosphamide 300 mg/m2/day IV for 3 days. See the prescribing information for fludarabine and cyclophosphamide for information on dose adjustment in renal impairment. Infuse BREYANZI 2 to 7 days after completion of lymphodepleting chemotherapy. Delay the infusion of BREYANZI if the patient has unresolved serious adverse events from preceding chemotherapies, active uncontrolled infection, or active graft-versus-host disease (GVHD). Premedication To minimize the risk of infusion reactions, premedicate the patient with acetaminophen (650 mg orally) and diphenhydramine (25-50 mg, IV or orally), or another H1-antihistamine, approximately 30 to 60 minutes prior to treatment with BREYANZI. Avoid prophylactic use of systemic corticosteroids, as they may interfere with the activity of BREYANZI. Receipt of BREYANZI • BREYANZI is shipped directly to the cell-associated lab or clinical pharmacy associated with the infusion center in the vapor phase of a liquid nitrogen shipper. • Confirm the patient’s identity with the patient identifiers on the shipper. • If the patient is not expected to be ready for administration before the shipper expires and the infusion site is qualified for onsite storage, transfer BREYANZI to onsite vapor phase of liquid nitrogen storage prior to preparation. • If the patient is not expected to be ready for administration before the shipper expires and the infusion site is not qualified for onsite storage, contact Bristol-Myers Squibb at 1-888-805-4555 to arrange for return shipment. Preparing BREYANZI Before thawing the vials • Confirm the patient’s identity with the patient identifiers on the RFI Certificate. • Read the RFI Certificate (affixed inside the shipper) for information on the number of syringes you will need to administer the CD8 and CD4 components (syringe labels are provided with the RFI Certificate). There is a separate RFI Certificate for each cell component. • Confirm tocilizumab and emergency equipment are available prior to infusion and during the recovery period. • Confirm the infusion time in advance and adjust the start time of BREYANZI thaw such that it will be available for infusion when the patient is ready. Thawing the vials • 1. Confirm the patient’s identity with the patient identifiers on the outer carton and on the syringe labels. Once the vials of CAR-positive viable T cells (CD8 component and CD4 component) are removed from frozen storage, the thaw must be carried to completion and the cells administered within 2 hours. • 2. Remove the CD8 component carton and CD4 component carton from the outer carton. • 3. Confirm the patient’s identity with the patient identifiers on the inner carton. • 4. Open each inner carton and visually inspect the vial(s) for damage. If the vials are damaged, contact Bristol-Myers Squibb at 1-888-805-4555. • 5. Confirm the patient’s identity with the patient identifiers on the vials. • 6. Carefully remove the vials from the cartons, place vials on a protective barrier pad, and thaw at room temperature until there is no visible ice in the vials. Thaw all of the vials at the same time. Keep the CD8 and CD4 components separate. Dose preparation • Prepare BREYANZI using sterile technique. • Based on the concentration of CAR-positive viable T cells for each component, more than one vial of each of the CD8 and CD4 components may be required to complete a dose. A separate syringe should be prepared for each CD8 or CD4 component vial received. Note: The volume to be drawn up and infused may differ for each component as indicated on the RFI Certificate. Do NOT draw up excess volume into the syringe. • Each vial contains 5 mL with a total extractable volume of 4.6 mL of CD8 or CD4 component T cells. The RFI Certificate for each component indicates the volume (mL) of cells to be drawn up into each syringe. Use the smallest Luer-lock tip syringe necessary (1, 3, or 5 mL) to draw up the specified volume from each vial. A 5 mL syringe should not be used for volumes less than 3 mL. • 7. Prepare the syringe(s) of the CD8 component first. Affix the CD8 syringe labels to the syringe(s) prior to pulling the required volume into the syringe(s). Note: It is important to confirm that the volume drawn up for each component matches the volume specified in the respective RFI Certificate. Do NOT draw up excess volume into the syringe. Withdrawal of the required volume of cells from each vial into a separate syringe should be carried out using the following instructions: • 8. Hold the thawed vial(s) upright and gently invert the vial(s) 5 times to mix the cell product. If any clumping is apparent, continue to invert the vial(s) until clumps have dispersed and cells appear to be evenly resuspended. • 9. Visually inspect the thawed vial(s) for damage or leaks. Do not use if the vial is damaged or if the clumps do not disperse; contact Bristol-Myers Squibb at 1-888-805-4555. The liquid in the vials should be slightly opaque to opaque, colorless to yellow or brownish-yellow. • 10. Remove the polyaluminum cover (if present) from the bottom of the vial and swab the septum with an alcohol wipe. Allow to air dry before proceeding. Note: The absence of the polyaluminum cover does not impact the sterility of the vial. • 11. Keeping the vial(s) upright, cut the seal on the tubing line on the top of the vial immediately above the filter to open the air vent on the vial. Note: Be careful to select the correct tubing line with the filter. Cut ONLY the tubing with a filter. • 12. Hold a 20-gauge, 1-1 ½ inch needle, with the opening of the needle tip away from the retrieval port septum. • a. Insert the needle into the septum at a 45°- 60° angle to puncture the retrieval port septum. • b. Increase the angle of the needle gradually as the needle enters the vial. a b • 13. WITHOUT drawing air into the syringe, slowly withdraw the target volume (as specified in the RFI Certificate). Carefully inspect the syringe for signs of debris prior to proceeding. If there is debris, contact Bristol-Myers Squibb at 1-888-805-4555. • 14. Verify that the volume of CD8/CD4 component matches the volume specified for the relevant component in the RFI Certificate. Once the volume is verified, remove the syringe/needle from the vial, carefully detach the needle from the syringe and cap the syringe. • 15. Continue to keep the vial horizontal and return it to the carton to avoid leaking from the vial. • 16. Dispose of any unused portion of BREYANZI (according to local biosafety guidelines). • 17. Repeat the process steps 7-16 for the CD4 Component. • 18. Transport the labeled CD8 and CD4 syringes to the bedside by placing with protective barrier pad inside an insulated room temperature container. Image Image Image Image Image Image Image Image Image Image BREYANZI Administration • Do NOT use a leukodepleting filter. • Confirm tocilizumab and emergency equipment are available prior to infusion and during the recovery period. • Confirm the patient’s identity matches the patient identifiers on the syringe label. • Once BREYANZI has been drawn into syringes, proceed with administration as soon as possible. The total time from removal from frozen storage to patient administration should not exceed 2 hours as indicated by the time entered on the syringe label. 19. Use intravenous normal saline to flush all the infusion tubing prior to and after each CD8 or CD4 component administration. 20. Administer the entire volume of the CD8 component intravenously at an infusion rate of approximately 0.5 mL/minute, using the closest port or Y-arm. Note: The time for infusion will vary but will usually be less than 15 minutes for each component. 21. If more than one syringe is required for a full cell dose of the CD8 component, administer the volume in each syringe consecutively without any time between administering the contents of the syringes (unless there is a clinical reason (e.g., infusion reaction) to hold the dose). 22. After the CD8 component has been administered, flush the tubing with normal saline, using enough volume to clear the tubing and the length of the IV catheter. 23. Administer the CD4 component second, immediately after administration of the CD8 component is complete, using steps 1-4, as described for the CD8 component. Following administration of the CD4 component, flush the tubing with normal saline, using enough volume to clear the tubing and the length of the IV catheter. BREYANZI contains human blood cells that are genetically modified with replication-incompetent, self-inactivating lentiviral vector. Follow universal precautions and local biosafety guidelines applicable for the handling and disposal, to avoid potential transmission of infectious diseases. Monitoring • Monitor patients daily for at least 7 days following BREYANZI infusion for signs and symptoms of CRS and neurologic toxicities. • Instruct patients to remain within proximity of a healthcare facility for at least 2 weeks following infusion. • Advise patients to avoid driving for at least 2 weeks following infusion. 2.3 Management of Severe Adverse Reactions Cytokine Release Syndrome Identify cytokine release syndrome (CRS) based on clinical presentation [see Warnings and Precautions (5.1)]. Evaluate for and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, manage according to the recommendations in Table 2. Physicians may also consider management per current practice guidelines. Patients who experience Grade 2 or higher CRS (e.g., hypotension not responsive to fluids, or hypoxia requiring supplemental oxygenation) should be monitored with continuous cardiac telemetry and pulse oximetry. For patients experiencing severe CRS, consider performing an echocardiogram to assess cardiac function. For severe or life-threatening CRS, consider intensive-care supportive therapy. If concurrent neurologic toxicity is suspected during CRS, administer: • Corticosteroids according to the more aggressive intervention based on the CRS and neurologic toxicity grades in Tables 2 and 3 • Tocilizumab according to the CRS grade in Table 2 • Antiseizure medication according to the neurologic toxicity in Table 3 Table 2: CRS Grading and Management Guidance a Lee criteria for grading CRS (Lee et al, 2014). b If corticosteroids are initiated, continue corticosteroids for at least 3 doses or until complete resolution of symptoms, and consider corticosteroid taper. CRS Gradea Tocilizumab Corticosteroidsb Grade 1 Fever If less than 72 hours after infusion, consider tocilizumab 8 mg/kg IV over 1 hour (not to exceed 800 mg). If 72 hours or more after infusion, treat symptomatically. If less than 72 hours after infusion, consider dexamethasone 10 mg IV every 24 hours. If 72 hours or more after infusion, treat symptomatically. Grade 2 Symptoms require and respond to moderate intervention. Oxygen requirement less than 40% FiO2, or hypotension responsive to fluids or low dose of one vasopressor, or Grade 2 organ toxicity. Administer tocilizumab 8 mg/kg IV over 1 hour (not to exceed 800 mg). Repeat tocilizumab every 8 hours as needed if not responsive to intravenous fluids or increasing supplemental oxygen. Limit to a maximum of 3 doses in a 24-hour period; maximum total of 4 doses. If less than 72 hours after infusion, administer dexamethasone 10 mg IV every 12‑24 hours. If 72 hours or more after infusion, consider dexamethasone 10 mg IV every 12‑24 hours. If no improvement within 24 hours or rapid progression, repeat tocilizumab and escalate dose and frequency of dexamethasone (10‑20 mg IV every 6 to 12 hours). If no improvement or continued rapid progression, maximize dexamethasone, switch to high-dose methylprednisolone 2 mg/kg if needed. After 2 doses of tocilizumab, consider alternative immunosuppressants. Do not exceed 3 doses tocilizumab in 24 hours, or 4 doses in total. Grade 3 Symptoms require and respond to aggressive intervention. Oxygen requirement greater than or equal to 40% FiO2, or hypotension requiring high-dose or multiple vasopressors, or Grade 3 organ toxicity, or Grade 4 transaminitis. Per Grade 2. Administer dexamethasone 10 mg IV every 12 hours. If no improvement within 24 hours or rapid progression of CRS, repeat tocilizumab and escalate dose and frequency of dexamethasone (10-20 mg IV every 6 to 12 hours). If no improvement or continued rapid progression, maximize dexamethasone, switch to high-dose methylprednisolone 2 mg/kg if needed. After 2 doses of tocilizumab, consider alternative immunosuppressants. Do not exceed 3 doses tocilizumab in 24 hours, or 4 doses in total. Grade 4 Life-threatening symptoms. Requirements for ventilator support or continuous veno‑venous hemodialysis (CVVHD) or Grade 4 organ toxicity (excluding transaminitis). Per Grade 2. Administer dexamethasone 20 mg IV every 6 hours. If no improvement within 24 hours or rapid progression of CRS, escalate tocilizumab and corticosteroid use. If no improvement or continued rapid progression, maximize dexamethasone, switch to high-dose methylprednisolone 2 mg/kg if needed. After 2 doses of tocilizumab, consider alternative immunosuppressants. Do not exceed 3 doses tocilizumab in 24 hours, or 4 doses in total. Neurologic Toxicity Monitor patients for signs and symptoms of neurologic toxicities (Table 3). Rule out other causes of neurologic symptoms. Provide intensive care supportive therapy for severe or life-threatening neurologic toxicities. If neurologic toxicity is suspected, manage according to the recommendations in Table 3. Physicians may also consider management per current practice guidelines. If concurrent CRS is suspected during neurologic toxicity, administer: • Corticosteroids according to the more aggressive intervention based on the CRS and neurologic toxicity grades in Tables 2 and 3 • Tocilizumab according to the CRS grade in Table 2 • Antiseizure medication according to the neurologic toxicity in Table 3 Table 3: Neurologic Toxicity (NT) Grading and Management Guidance NT Gradea Corticosteroids and Antiseizure Medication a NCI CTCAE criteria for grading neurologic toxicities, version 4.03. Grade 1 Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis. If 72 hours or more after infusion, observe. If less than 72 hours after infusion, consider dexamethasone 10 mg IV every 12 to 24 hours for 2 to 3 days. Grade 2 Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis. Dexamethasone 10 mg IV every 12 hours for 2-3 days, or longer for persistent symptoms. Consider taper for a total steroid exposure of greater than 3 days. If no improvement after 24 hours or worsening of neurologic toxicity, increase the dose and/or frequency of dexamethasone up to a maximum of 20 mg IV every 6 hours. If no improvement after another 24 hours, rapidly progressing symptoms, or life-threatening complications arise, give methylprednisolone (2 mg/kg loading dose, followed by 2 mg/kg divided 4 times a day; taper within 7 days). Grade 3 Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis. Dexamethasone 10 to 20 mg IV every 8 to 12 hours. Steroids are not recommended for isolated Grade 3 headaches. If no improvement after 24 hours or worsening of neurologic toxicity, escalate to methylprednisolone (dose and frequency as per Grade 2). If cerebral edema is suspected, consider hyperventilation and hyperosmolar therapy. Give high-dose methylprednisolone (1-2 g, repeat every 24 hours if needed; taper as clinically indicated) and cyclophosphamide 1.5 g/m2. Grade 4 Start non-sedating, antiseizure medicines (e.g., levetiracetam) for seizure prophylaxis. Dexamethasone 20 mg IV every 6 hours. If no improvement after 24 hours or worsening of neurologic toxicity, escalate to methylprednisolone (dose and frequency as per Grade 2). If cerebral edema is suspected, consider hyperventilation and hyperosmolar therapy. Give high-dose methylprednisolone (1-2 g, repeat every 24 hours if needed; taper as clinically indicated), and cyclophosphamide 1.5 g/m2.

BREYANZI is a cell suspension for infusion.

A single dose of BREYANZI contains CAR-positive viable T cells that consist of CD8 and CD4 components, with each component supplied separately in single-dose vials [see Dosage and Administration (2.1)].

More than one vial of each of the CD8 component and/or CD4 component may be needed to achieve the dose of BREYANZI.

Each vial contains between 6.9 × 10⁶and 322 × 10⁶ CAR-positive viable T cells in 4.6 mL cell suspension (between 1.5 × 10⁶and 70 x 10⁶ CAR-positive viable T cells/mL).

The infusion volume is calculated based on the concentration of cryopreserved drug product CAR-positive viable T cells. The volume may differ for each component infused. See the RFI Certificate for details [see How Supplied/Storage and Handling (16)].

Drug interactions

7.1 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. HIV and…

References

Source: DailyMed, U.S. National Library of Medicine. Additional information compiled from online sources.

Important: The information on this page is provided for reference only and is not a substitute for diagnosis, prescribing, or treatment guidance from a doctor or pharmacist.

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