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Indications

BLINCYTO® (blinatumomab) is indicated for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adult and pediatric patients. ... Read More 

BLINCYTO® is indicated for the treatment of relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients.

Important Safety Information Prescribing Information Medication Guide Indications Patient Site Connect with a BLINCYTO® rep

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Adult safety profile

MRD(+)

Majority of the most common adverse reactions ( ≥ 10% incidence) were mild to moderate1,2

Most common adverse reactions (≥ 10%) (N=137)*

Adverse reaction Any Grade†
n (%)		 Grade ≥ 3†
n (%)
Blood and lymphatic system disorders
Neutropenia‡ 21 (15) 21 (15)
Leukopenia§ 19 (14) 13 (9)
Thrombocytopenia** 14 (10) 8 (6)
Cardiac disorders
Arrhythmia†† 17 (12) 3 (2)
General disorders and administration-site conditions
Pyrexia‡‡ 125 (91) 9 (7)
Chills 39 (28) 0 (0)
Infections and infestations
Infections – pathogen unspecified 53 (39) 11 (8)
Injury, poisoning, and procedural complications
Infusion-related reaction§§ 105 (77) 7 (5)
Investigations
Decreased immunoglobulins*** 25 (18) 7 (5)
Weight increased 14 (10) 1 (<1)
Hypertransaminasemia††† 13 (9) 9 (7)
Musculoskeletal and connective tissue disorders
Back pain 16 (12) 1 (<1)
Nervous system disorders
Headache‡‡‡‡ 54 (39) 5 (4)
Tremor‡‡‡, ‡‡‡‡ 43 (31) 6 (4)
Aphasia‡‡‡‡ 16 (12) 1 (<1)
Dizziness‡‡‡‡ 14 (10) 1 (<1)
Encephalopathy§§§, ‡‡‡‡ 14 (10) 6 (4)
Psychiatric disorders
Insomnia****, ‡‡‡‡ 24 (18) 1 (<1)
Respiratory, thoracic, and mediastinal disorders
Cough 18 (13) 0 (0)
Skin and subcutaneous tissue disorders
Rash†††† 22 (16) 1 (<1)
Vascular disorders
Hypotension 19 (14) 1 (<1)
  • Adverse reactions of Grade 3 or higher were reported in 64% of patients1
  • The most common adverse reactions (>=20%) were pyrexia (91%), infusion-related reactions (77%), headache (39%), infections (pathogen unspecified, 39%), tremor (31%), and chills (28%). Serious adverse reactions were reported in 61% of patients.1
  • In the BLAST study, neurologic events and cytokine release syndrome (CRS) were clinically managed with treatment interruption and dexamethasone1
  • There were 2 fatal adverse reactions that occurred within 30 days of the end of BLINCYTO treatment (atypical pneumonia and subdural hemorrhage).1

*The safety of BLINCYTO® in patients with MRD(+) B-cell precursor ALL was evaluated in 2 single-arm studies with a total of 137 patients.1

†Grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, in which Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe or medically significant but not immediately life-threatening, and Grade 4 is life-threatening.1,2

‡Neutropenia includes febrile neutropenia, neutropenia, and neutrophil count decreased.1

§Leukopenia includes leukopenia and white blood cell count decreased.1

**Thrombocytopenia includes platelet count decreased and thrombocytopenia.1

††Arrhythmia includes bradycardia, sinus arrhythmia, sinus bradycardia, sinus tachycardia, tachycardia, and ventricular extrasystoles.1

‡‡Pyrexia includes body temperature increased and pyrexia.1

§§Infusion-related reaction is a composite term that includes the term infusion-related reaction and the following events occurring within the first 48 hours of infusion and the event lasted ≤ 2 days: cytokine release syndrome, eye swelling, hypertension, hypotension, myalgia, periorbital edema, pruritus generalized, pyrexia, and rash.1

***Decreased immunoglobulins includes blood immunoglobulin A decreased, blood immunoglobulin G decreased, blood immunoglobulin M decreased, hypogammaglobulinemia, hypoglobulinemia, and immunoglobulins decreased.1

†††Hypertransaminasemia includes alanine aminotransferase increased, aspartate aminotransferase increased, and hepatic enzyme increased.1

‡‡‡Tremor includes essential tremor, intention tremor, and tremor.1

§§§Encephalopathy includes cognitive disorder, depressed level of consciousness, disturbance in attention, encephalopathy, lethargy, leukoencephalopathy, memory impairment, somnolence, and toxic encephalopathy.1

****Insomnia includes initial insomnia, insomnia, and terminal insomnia.1

††††Rash includes dermatitis contact, eczema, erythema, rash, and rash maculopapular.1

‡‡‡‡May represent ICANS.1

ALL, acute lymphoblastic leukemia; CRS, cytokine release syndrome; MRD, measurable or minimal residual disease.

R/R: The TOWER landmark study

Adverse events occurring at ≥ 10% incidence for any Grade or ≥ 5% incidence for Grade 3 or higher in BLINCYTO®-treated patients in first cycle of therapy1

Adverse event BLINCYTO® (N=267) SOC Chemotherapy (N=109)
Any Grade* n (%) ≥ Grade 3* n (%) Any Grade* n (%) ≥ Grade 3* n (%)
Blood and lymphatic system disorders
Neutropenia† 84 (31) 76 (28) 67 (61) 61 (56)
Anemia‡ 68 (25) 52 (19) 45 (41) 37 (34)
Thrombocytopenia§ 57 (21) 47 (18) 42 (39) 40 (37)
Leukopenia** 21 (8) 18 (7) 9 (8) 9 (8)
Cardiac disorder
Arrhythmia†† 37 (14) 5 (2) 18 (17) 0 (0)
General disorders and administration-site conditions
Pyrexia 147 (55) 15 (6) 43 (39) 4 (4)
Edema‡‡ 48 (18) 3 (1) 20 (18) 1 (1)
Immune system disorders
Cytokine release syndrome§§ 37 (14) 8 (3) 0 (0) 0 (0)
Infections and infestations
Infections — pathogen unspecified 74 (28) 40 (15) 50 (46) 35 (32)
Bacterial infectious disorders 38 (14) 19 (7) 35 (32) 21 (19)
Viral infectious disorders 30 (11) 4 (1) 14 (13) 0 (0)
Fungal infectious disorders 27 (10) 13 (5) 15 (14) 9 (8)
Injury, poisoning, and procedural complications
Infusion-related reaction*** 79 (30) 9 (3) 9 (8) 1 (1)
Investigations
Hypertransaminasemia††† 40 (15) 22 (8) 13 (12) 7 (6)
Nervous system disorders
Headache§§§ 61 (23) 1 (<1) 30 (28) 3 (3)
Skin and subcutaneous tissue disorders
Rash‡‡‡ 31 (12) 2 (1) 21 (19) 0 (0)
  • The most common adverse reactions (≥ 20%) in the BLINCYTO arm were infections (bacterial and pathogen unspecified), pyrexia, headache, infusion-related reactions, anemia, febrile neutropenia, thrombocytopenia, and neutropenia. Serious adverse reactions were reported in 62% of patients.
  • Adverse reactions of Grade 3 or higher were reported in 87% of patients.
  • Fatal adverse events occurred in 16% of patients. The majority of the fatal events were infections.

*Grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.1

†Neutropenia includes agranulocytosis, febrile neutropenia, neutropenia, and neutrophil count decreased.1

‡Anemia includes anemia and hemoglobin decreased.1

§Thrombocytopenia includes platelet count decreased and thrombocytopenia.1

**Leukopenia includes leukopenia and white blood cell count decreased.1

††Arrhythmia includes arrhythmia, atrial fibrillation, atrial flutter, bradycardia, sinus bradycardia, sinus tachycardia, supraventricular tachycardia, and tachycardia.1

‡‡Edema includes face edema, fluid retention, edema, edema peripheral, peripheral swelling, and swelling face.1

§§Cytokine release syndrome includes cytokine release syndrome and cytokine storm.1

***Infusion-related reaction is a composite term that includes the term infusion-related reaction and the following events occurring with the first 48 hours of infusion and the event lasted ≤ 2 days: pyrexia, cytokine release syndrome, hypotension, myalgia, acute kidney injury, hypertension, and rash erythematous.1

†††Hypertransaminasemia includes alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, and transaminases increased.1

‡‡‡Rash includes erythema, rash, rash erythematous, rash generalized, rash macular, rash maculopapular, rash pruritic, skin exfoliation, and toxic skin eruption.1

§§§May represent ICANs.1


R/R: Real-World Evidence study


Safety profile of BLINCYTO® in a real-world evidence study3

Variables n=159
n (%)
BLINCYTO® dosing
Could not titrate to full dose due to tolerance 5 (3.1)
Achieved full dose (9 mcg/kg for 1 week and 28 mcg/day thereafter) 154 (96.9)
Dose interruptions
0 120 (75.5)
1 29 (18.2)
2 7 (4.4)
3 3 (1.9)
Discontinuation due to adverse events
No 149 (93.7)
Yes 10 (6.3)
Any adverse event (max CRS, neurotoxicity, hepatotoxicity)
Grades 1–2 62 (39.0)
Grades ≥ 3 34 (21.4)
CRS
Grades 1–2 56 (35.9)
Grades ≥ 3 6 (3.8)
Missing 3
Neurological adverse events (max seizure, headache, encephalopathy, stroke)
Grades 1–2 22 (14.0)
Grades ≥ 3 12 (7.6)
Missing 2
Encephalopathy
Grades 1–2 8 (5.1)
Grades ≥ 3 10 (6.4)
Missing 2
Headache
Grades 1–2 18 (11.4)
Grades ≥ 3 2 (1.3)
Missing 1
Seizure
Grades 1–2 1 (0.6)
Grades ≥ 3 1 (0.6)
Missing 1
Hepatotoxicity (max transaminases, VOD, hyperbilirubinemia)
Grades 1–2 28 (17.8)
Grades ≥ 3 21 (13.4)
Missing 2
Transaminases
Grades 1–2 22 (13.9)
Grades ≥ 3 18 (11.4)
Missing 1
Hyperbilirubinemia
Grades 1–2 13 (8.3)
Grades ≥ 3 4 (2.6)
Missing 3
VOD
Grades 1–2 1 (0.6)
Grades ≥ 3 1 (0.6)
Missing 1

  • Grade ≥ 3 AEs demonstrated in the real-world evidence study were consistent with the clinical study data1,3

AE, adverse event; CRS, cytokine release syndrome; SOC, standard-of-care; VOD, veno-occlusive disease.

R/R Ph(+): ALCANTARA study

The most common treatment-emergent adverse events (TEAEs) were pyrexia, febrile neutropenia, and headache4


Adverse events (regardless of causality)4


 Grade*

Any 1 to 2 3 4
Event No. % No. % No. % No. %
Patients with AEs 45 100 45 100 33 73 16 36
AEs of Grade ≥ 3 occurring in ≥ 5% of patients*
Pyrexia 26 58 24 53 5 11 0 0
Febrile neutropenia 18 40 9 20 12 27 0 0
Headache 14 31 13 29 3 7 0 0
Anemia 13 29 9 20 7 16 1 2
Thrombocytopenia 10 22 4 9 5 11 7 16
Pain 7 16 4 9 4 9 0 0
Increased aspartate aminotransferase 6 13 3 7 3 7 2 4
Increased alanine aminotransferase 5 11 1 2 5 11 0 0
Device-related infection 5 11 3 7 3 7 0 0
Neutropenia 3 7 0 0 0 0 3 7
  • No incidents of Grade ≥ 3 CRS were reported4
  • One patient died from septic shock, which was considered treatment-related by the investigator4

*Grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.4

Neurologic events were generally mild to moderate and were managed with dosage adjustments and/or treatment interruption4


Neurologic events (regardless of causality)4


 Grade*

Any 1 to 2 3 4
Event No. % No. % No. % No. %
Patients with neurologic events 21 47 20 44 3 7 0 0
Neurologic events occurring in two or more patients
Paresthesia 6 13 6 13 0 0 0 0
Confusional state 5 11 5 11 0 0 0 0
Dizziness 4 9 4 9 0 0 0 0
Tremor 4 9 4 9 0 0 0 0
Aphasia 2 4 1 2 1 2 0 0
Cerebellar syndrome 2 4 2 4 0 0 0 0
Memory impairment 2 4 2 4 0 0 0 0
Nervous system disorder 2 4 1 2 1 2 0 0
  • Neurologic events were reported in 21 (47%) patients; these were mild or moderate in all but 3 patients4
  • Three patients experienced a Grade 3 neurologic event (aphasia, hemiplegia, and nervous system disorder or depressed level of consciousness)4
  • One patient required treatment interruption due to neurologic events (aphasia)4

†Grading based on NCI CTCAE version 4.0.4

AE, adverse event; CRS, cytokine release syndrome.

See more

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

  • Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue
    BLINCYTO® and treat with corticosteroids as recommended.
  • Neurological toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS) which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended.
Contraindications

BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions
  • Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in 15% of patients with R/R ALL and in 7% of patients with MRD-positive ALL. The median time to onset of CRS is 2 days after the start of infusion and the median time to resolution of CRS was 5 days among cases that resolved. Closely monitor and advise patients to contact their healthcare professional for signs and symptoms of serious adverse events such as fever, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), and disseminated intravascular coagulation (DIC). The manifestations of CRS after treatment with BLINCYTO® overlap with those of infusion reactions, capillary leak syndrome, and hemophagocytic histiocytosis/macrophage activation syndrome. If severe CRS occurs, interrupt BLINCYTO® until CRS resolves. Discontinue BLINCYTO® permanently if life-threatening CRS occurs. Administer corticosteroids for severe or life-threatening CRS.
  • Neurological Toxicities, including Immune Effector Cell-Associated Neurotoxicity Syndrome: BLINCYTO can cause serious or life-threatening neurologic toxicity, including ICANS. The incidence of neurologic toxicities in clinical trials was approximately 65%. The median time to the first event was within the first 2 weeks of BLINCYTO® treatment. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Grade 3 or higher neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. The majority of neurologic toxicities resolved following interruption of BLINCYTO, but some resulted in treatment discontinuation.

    • The incidence of signs and symptoms consistent with ICANS in clinical trials was 7.5%. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Monitor patients for signs or symptoms of neurological toxicities, including ICANS, and interrupt or discontinue BLINCYTO® as outlined in the PI.

  • Infections: Approximately 25% of patients receiving BLINCYTO® in clinical trials experienced serious infections such as sepsis, pneumonia,
    bacteremia, opportunistic infections, and catheter-site infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics
    and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately,
    including interruption or discontinuation of BLINCYTO® as needed.
  • Tumor Lysis Syndrome (TLS), which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic
    cytoreduction and on-treatment hydration, should be used during BLINCYTO® treatment. Monitor patients for signs and symptoms of TLS and
    interrupt or discontinue BLINCYTO® as needed to manage these events.
  • Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters (including,
    but not limited to, white blood cell count and absolute neutrophil count) during BLINCYTO® infusion and interrupt BLINCYTO® if prolonged
    neutropenia occurs.
  • Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures and ICANS, patients receiving BLINCYTO® are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO® is being administered.
  • Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO® treatment with a median time to onset of 3
    days. In patients receiving BLINCYTO®, although the majority of these events were observed in the setting of CRS, some cases of elevated liver
    enzymes were observed outside the setting of CRS, with a median time to onset of 19 days. Grade 3 or greater elevations in liver enzymes occurred in approximately 7% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST,
    gamma-glutamyl transferase, and TBILI prior to the start of and during BLINCYTO® treatment. BLINCYTO® treatment should be interrupted if
    transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
  • Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO® in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO® and dexamethasone as needed.
  • Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing
    leukoencephalopathy have been observed in patients receiving BLINCYTO®, especially in patients previously treated with cranial irradiation and
    antileukemic chemotherapy.
  • Preparation and administration errors have occurred with BLINCYTO® treatment. Follow instructions for preparation (including admixing) and
    administration in the PI strictly to minimize medication errors (including underdose and overdose).
  • Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO® treatment, during
    treatment, and until immune recovery following last cycle of BLINCYTO®.
  • Benzyl Alcohol Toxicity in Neonates: Serious adverse reactions, including fatal reactions and the “gasping syndrome”, have been reported in very low birth weight (VLBW) neonates born weighing less than 1500 g, and early preterm neonates (infants born less than 34 weeks gestational age) who received intravenous drugs containing benzyl alcohol as a preservative. Early preterm VLBW neonates may be more likely to develop these reactions, because they may be less able to metabolize benzyl alcohol.

    • Use the preservative-free preparations of BLINCYTO® where possible in neonates. When prescribing BLINCYTO® (with preservative) for neonatal patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO® (with preservative), other products containing benzyl alcohol or other excipients (e.g., ethanol, propylene glycol) which compete with benzyl alcohol for the same metabolic pathway.

    Monitor neonatal patients receiving BLINCYTO® (with preservative) for new or worsening metabolic acidosis. The minimum amount of benzyl
    alcohol at which serious adverse reactions may occur in neonates is not known. The BLINCYTO® 7-Day bag (with preservative) contains 7.4 mg of benzyl alcohol per mL.

  • Embryo-Fetal Toxicity: Based on its mechanism of action, BLINCYTO® may cause fetal harm when administered to a pregnant woman. Advise
    pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with
    BLINCYTO® and for 48 hours after the last dose.
Adverse Reactions
  • The most common adverse reactions (≥ 20%) are pyrexia, infusion-related reactions, infections (pathogen unspecified), headache, neutropenia,
    anemia, and thrombocytopenia.
Dosage and Administration Guidelines
  • BLINCYTO® is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
  • It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
INDICATIONS
  • BLINCYTO® (blinatumomab) is indicated for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adult and pediatric patients.
  • BLINCYTO® is indicated for the treatment of relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients.

Please see BLINCYTO® full Prescribing Information, including BOXED WARNINGS.

BLINCYTO® is a registered trademark of Amgen Inc.

See more

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and
NEUROLOGICAL TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED
NEUROTOXICITY SYNDROME

  • Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® and treat with corticosteroids as recommended.
  • Neurological toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS) which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended.
Contraindications
References: 1. BLINCYTO® (blinatumomab) prescribing information, Amgen. 2. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Accessed March 01, 2024. 3. Data on file, Amgen; 2021. 4. Martinelli G, Boissel N, Chevallier P, et al. Complete hematologic and molecular response in adult patients with relapsed/refractory Philadelphia chromosome–positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. J Clin Oncol. 2017;35:1795-1802.
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