Blincyto Side Effects Center

Last updated on RxList: 6/2/2022
Blincyto Side Effects Center

What Is Blincyto?

Blincyto (blinatumomab) for injection is a bispecific CD19-directed CD3 T- cell engager indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

What Are Side Effects for Blincyto?

Common side effects of Blincyto include:

Dosage for Blincyto

Hospitalization is recommended for the first 9 days of the first cycle and the first 2 days of the second cycle of treatment with Blincyto. A single cycle of treatment with Blincyto consists of 4 weeks of continuous intravenous infusion followed by a 2-week treatment-free interval.

What Drugs, Substances, or Supplements Interact with Blincyto?

Blincyto may interact with warfarin, cyclosporine, or other drugs. Tell your doctor all medications and supplements you use.

Blincyto During Pregnancy and Breastfeeding

During pregnancy, Blincyto should only be administered if prescribed. It may harm a fetus. It is unknown if Blincyto passes into breast milk. Breastfeeding while using Blincyto is not recommended.

Additional Information

Our Blincyto (blinatumomab) for injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

What is leukemia? See Answer
Blincyto Consumer Information

Some side effects may occur during the injection. Tell your caregiver right away if you feel weak, nauseated, light-headed, tired, chilled or feverish, or you have a headache, muscle pain, skin rash, wheezing, trouble breathing, or swelling in your face.

Get emergency medical help if you signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Also tell your caregivers or seek emergency medical attention if you have signs of life-threatening nerve problems, such as:

  • slurred speech, confusion;
  • problems with balance;
  • a seizure (convulsions); or
  • loss of consciousness.

A serious side effect of blinatumomab is called cytokine release syndrome (CRS). Tell your caregivers right away if you have signs of this condition: fever, chills, trouble breathing, body aches, vomiting, diarrhea, or feeling light-headed. Your caregivers will have medication available to quickly treat CRS if it occurs.

Call your doctor at once if you have:

  • severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;
  • low potassium--leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling;
  • low blood cell counts--fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath; or
  • signs of tumor cell breakdown--confusion, weakness, muscle cramps, nausea, vomiting, fast or slow heart rate, decreased urination, tingling in your hands and feet or around your mouth.

Common side effects may include:

  • reactions during the injection;
  • low blood cell counts;
  • fever, infections; or
  • headache.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Blincyto (Blinatumomab for Injection)

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Blincyto Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Cytokine Release Syndrome [see WARNINGS AND PRECAUTIONS]
  • Neurological Toxicities [see WARNINGS AND PRECAUTIONS]
  • Infections [see WARNINGS AND PRECAUTIONS]
  • Tumor Lysis Syndrome [see WARNINGS AND PRECAUTIONS]
  • Neutropenia and Febrile Neutropenia [see WARNINGS AND PRECAUTIONS]
  • Effects on Ability to Drive and Use Machines [see WARNINGS AND PRECAUTIONS]
  • Elevated Liver Enzymes [see WARNINGS AND PRECAUTIONS]
  • Pancreatitis [see WARNINGS AND PRECAUTIONS]
  • Leukoencephalopathy [see WARNINGS AND PRECAUTIONS]

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.

MRD-Positive B-Cell Precursor ALL

The safety of BLINCYTO in patients with MRD-positive B-cell precursor ALL was evaluated in two single-arm clinical studies in which 137 patients were treated with BLINCYTO. The median age of the study population was 45 years (range: 18 to 77 years).

The most common adverse reactions (≥ 20%) were pyrexia, infusion related reactions, headache, infections (pathogen unspecified), tremor, and chills. Serious adverse reactions were reported in 61% of patients. The most common serious adverse reactions (≥ 2%) included pyrexia, tremor, encephalopathy, aphasia, lymphopenia, neutropenia, overdose, device related infection, seizure, and staphylococcal infection. Adverse reactions of Grade 3 or higher were reported in 64% of patients. Discontinuation of therapy due to adverse reactions occurred in 17% of patients; neurologic events were the most frequently reported reasons for discontinuation. There were 2 fatal adverse reactions that occurred within 30 days of the end of BLINCYTO treatment (atypical pneumonia and subdural hemorrhage).

Table 8 summarizes the adverse reactions occurring at a ≥ 10% incidence for any grade or ≥ 5% incidence for Grade 3 or higher.

Table 8. Adverse Reactions Occurring at ≥ 10% Incidence for Any Grade or ≥ 5% Incidence for Grade 3 or Higher in BLINCYTO-Treated Patients with MRD-Positive B-cell Precursor ALL

Adverse Reaction BLINCYTO
(N=137)
Any Grade*
n (%)
Grade ≥
3* n (%)
Blood and lymphatic system disorders
  Neutropenia1 21 (15) 21 (15)
  Leukopenia2 19 (14) 13 (9)
  Thrombocytopenia3 14 (10) 8 (6)
Cardiac disorders
  Arrhythmia4 17 (12) 3 (2)
General disorders and administration site conditions
  Pyrexia5 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 reaction6 105 (77) 7 (5)
Investigations
  Decreased immunoglobulins7 25 (18) 7 (5)
  Weight increased 14 (10) 1 (<1)
  Hypertransaminasemia8 13 (9) 9 (7)
Musculoskeletal and connective tissue disorders
  Back pain 16 (12) 1 (<1)
Nervous system disorders
  Headache 54 (39) 5 (4)
  Tremor9 43 (31) 6 (4)
  Aphasia 16 (12) 1 (<1)
  Dizziness 14 (10) 1 (<1)
  Encephalopathy10 14 (10) 6 (4)
Psychiatric disorders
  Insomnia11 24 (18) 1 (<1)
Respiratory, thoracic and mediastinal disorders
  Cough 18 (13) 0 (0)
Skin and subcutaneous tissue disorders
  Rash12 22 (16) 1 (<1)
Vascular disorders
  Hypotension 19 (14) 1 (<1)
* Grading based on NCI Common Terminology for Adverse Events (CTCAE) version 4.0.
1 Neutropenia includes febrile neutropenia, neutropenia, and neutrophil count decreased.
2 Leukopenia includes leukopenia and white blood cell count decreased.
3 Thrombocytopenia includes platelet count decreased and thrombocytopenia.
4 Arrhythmia includes bradycardia, sinus arrhythmia, sinus bradycardia, sinus tachycardia, tachycardia and ventricular extrasystoles.
5 Pyrexia includes body temperature increased and pyrexia.
6 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: cytokine release syndrome, eye swelling, hypertension, hypotension, myalgia, periorbital edema, pruritus generalized, pyrexia, and rash.
7 Decreased immunoglobulins includes blood immunoglobulin A decreased, blood immunoglobulin G decreased, blood immunoglobulin M decreased, hypogammaglobulinemia, hypoglobulinemia, and immunoglobulins decreased.
8 Hypertransaminasemia includes alanine aminotransferase increased, aspartate aminotransferase increased, and hepatic enzyme increased.
9 Tremor includes essential tremor, intention tremor, and tremor.
10 Encephalopathy includes cognitive disorder, depressed level of consciousness, disturbance in attention, encephalopathy, lethargy, leukoencephalopathy, memory impairment, somnolence, and toxic encephalopathy.
11 Insomnia includes initial insomnia, insomnia, and terminal insomnia.
12 Rash includes dermatitis contact, eczema, erythema, rash, and rash maculopapular.

Additional adverse reactions in patients with MRD-positive ALL that did not meet the threshold criteria for inclusion in Table 8 were:

Blood and lymphatic system disorders: anemia

General disorders and administration site conditions: edema peripheral, pain, and chest pain (includes chest pain and musculoskeletal chest pain)

Hepatobiliary disorders: blood bilirubin increased

Immune system disorders: hypersensitivity and cytokine release syndrome

Infections and infestations: viral infectious disorders, bacterial infectious disorders, and fungal infectious disorders

Injury, poisoning and procedural complications: medication error and overdose (includes overdose and accidental overdose)

Investigations: blood alkaline phosphatase increased

Musculoskeletal and connective tissue disorders: pain in extremity and bone pain

Nervous system disorders: seizure (includes seizure and generalized tonic-clonic seizure), speech disorder, and hypoesthesia

Psychiatric disorders: confusional state, disorientation, and depression

Respiratory, thoracic and mediastinal disorders: dyspnea and productive cough

Vascular disorders: hypertension (includes blood pressure increased and hypertension) flushing (includes flushing and hot flush), and capillary leak syndrome

Philadelphia Chromosome-Negative Relapsed Or Refractory B-Cell Precursor ALL

The safety of BLINCYTO was evaluated in a randomized, open-label, active-controlled clinical study (TOWER Study) in which 376 patients with Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL were treated with BLINCYTO (n = 267) or standard of care (SOC) chemotherapy (n = 109). The median age of BLINCYTO-treated patients was 37 years (range: 18 to 80 years), 60% were male, 84% were White, 7% Asian, 2% were Black or African American, 2% were American Indian or Alaska Native, and 5% were Multiple/Other.

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. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, sepsis, pneumonia, overdose, septic shock, CRS, bacterial sepsis, device related infection, and bacteremia. Adverse reactions of Grade 3 or higher were reported in 87% of patients. Discontinuation of therapy due to adverse reactions occurred in 12% of patients treated with BLINCYTO; neurologic events and infections were the most frequently reported reasons for discontinuation of treatment due to an adverse reaction. Fatal adverse events occurred in 16% of patients. The majority of the fatal events were infections.

The adverse reactions occurring at a ≥ 10% incidence for any grade or ≥ 5% incidence for Grade 3 or higher in the BLINCYTO-treated patients in first cycle of therapy are summarized in Table 9.

Table 9. Adverse Reactions Occurring at ≥ 10% Incidence for Any Grade or ≥ 5% Incidence for Grade 3 or Higher in BLINCYTO-treated Patients in First Cycle of Therapy

Adverse Reaction BLINCYTO
(N = 267)
Standard of Care (SOC)
Chemotherapy
(N = 109)
Any Grade*
n (%)
Grade ≥ 3*
n (%)
Any Grade*
n (%)
Grade ≥ 3*
n (%)
Blood and lymphatic system disorders
  Neutropenia1 84 (31) 76 (28) 67 (61) 61 (56)
  Anemia2 68 (25) 52 (19) 45 (41) 37 (34)
  Thrombocytopenia3 57 (21) 47 (18) 42 (39) 40 (37)
  Leukopenia4 21 (8) 18 (7) 9 (8) 9 (8)
Cardiac disorders
  Arrhythmia5 37 (14) 5 (2) 18 (17) 0 (0)
General disorders and administration site conditions
  Pyrexia 147 (55) 15 (6) 43 (39) 4 (4)
  Edema6 48 (18) 3 (1) 20 (18) 1 (1)
Immune system disorders
  Cytokine release syndrome7 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 reaction8 79 (30) 9 (3) 9 (8) 1 (1)
Investigations
  Hypertransaminasemia9 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
  Rash10 31 (12) 2 (1) 21 (19) 0 (0)
* Grading based on NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
1 Neutropenia includes agranulocytosis, febrile neutropenia, neutropenia, and neutrophil count decreased
2 Anemia includes anemia and hemoglobin decreased.
3 Thrombocytopenia includes platelet count decreased and thrombocytopenia.
4 Leukopenia includes leukopenia and white blood cell count decreased.
5 Arrhythmia includes arrhythmia, atrial fibrillation, atrial flutter, bradycardia, sinus bradycardia, sinus tachycardia, supraventricular tachycardia, and tachycardia.
6 Edema includes face edema, fluid retention, edema, edema peripheral, peripheral swelling, and swelling face
7 Cytokine release syndrome includes cytokine release syndrome and cytokine storm.
8 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.
9 Hypertransaminasemia includes alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, and transaminases increased.
10 Rash includes erythema, rash, rash erythematous, rash generalized, rash macular, rash maculo-papular, rash pruritic, skin exfoliation, and toxic skin eruption.

Selected laboratory abnormalities worsening from baseline Grade 0-2 to treatment-related maximal Grade 3-4 in first cycle of therapy are shown in Table 10.

Table 10. Selected Laboratory Abnormalities Worsening from Baseline Grade 0-2 to Treatment-related Maximal Grade 3-4* in First Cycle of Therapy

BLINCYTO
Grade 3 or 4 (%)
SOC Chemotherapy
Grade 3 or 4 (%)
Hematology
  Decreased lymphocyte count 80 83
  Decreased white blood cell count 53 97
  Decreased hemoglobin 29 43
  Decreased neutrophil count 57 68
  Decreased platelet count 47 85
Chemistry
  Increased ALT 11 11
  Increased bilirubin 5 4
  Increased AST 8 4
* Includes only patients who had both baseline and at least one laboratory measurement during first cycle of therapy available.

Relapsed Or Refractory B-Cell Precursor ALL

Other important adverse reactions from pooled relapsed or refractory B-cell precursor ALL studies were:

Blood and lymphatic system disorders: lymphadenopathy, hematophagic histiocytosis, and leukocytosis (includes leukocytosis and white blood cell count increased)

General disorders and administration site conditions: chills, chest pain (includes chest discomfort, chest pain, musculoskeletal chest pain, and non-cardiac chest pain), pain, body temperature increased, hyperthermia, and systemic inflammatory response syndrome

Hepatobiliary disorders: hyperbilirubinemia (includes blood bilirubin increased and hyperbilirubinemia)

Immune system disorders: hypersensitivity (includes hypersensitivity, anaphylactic reaction, angioedema, dermatitis allergic, drug eruption, drug hypersensitivity, erythema multiforme, and urticaria)

Injury, poisoning and procedural complications: medication error and overdose (includes overdose, medication error, and accidental overdose)

Investigations: weight increased, decreased immunoglobulins (includes immunoglobulins decreased, blood immunoglobulin A decreased, blood immunoglobulin G decreased, blood immunoglobulin M decreased, and hypogammaglobulinemia), blood alkaline phosphatase increased, and hypertransaminasemia

Metabolism and nutrition disorders: tumor lysis syndrome

Musculoskeletal and connective tissue disorders: back pain, bone pain, and pain in extremity

Nervous system disorders: tremor (resting tremor, intention tremor, essential tremor, and tremor), altered state of consciousness (includes altered state of consciousness, depressed level of consciousness, disturbance in attention, lethargy, mental status changes, stupor, and somnolence), dizziness, memory impairment, seizure (includes seizure, and atonic seizure), aphasia, cognitive disorder, speech disorder, hypoesthesia, encephalopathy, and cranial nerve disorders (trigeminal neuralgia, trigeminal nerve disorder, sixth nerve paralysis, cranial nerve disorder, facial nerve disorder, and facial paresis)

Psychiatric disorders: insomnia, disorientation, confusional state, and depression (includes depressed mood, depression, suicidal ideation, and completed suicide)

Respiratory, thoracic and mediastinal disorders: dyspnea (includes acute respiratory failure, dyspnea, dyspnea exertional, respiratory failure, respiratory distress, bronchospasm, bronchial hyperreactivity, tachypnea, and wheezing), cough, and productive cough

Vascular disorders: hypotension (includes blood pressure decreased, hypotension, hypovolemic shock, and circulatory collapse), hypertension (includes blood pressure increased, hypertension, and hypertensive crisis), flushing (includes flushing and hot flush), and capillary leak syndrome

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to blinatumomab with the incidence of antibodies to other products may be misleading.

The immunogenicity of BLINCYTO has been evaluated using either an electrochemiluminescence detection technology (ECL) or an enzyme-linked immunosorbent assay (ELISA) screening immunoassay for the detection of binding anti-blinatumomab antibodies. For patients whose sera tested positive in the screening immunoassay, an in vitro biological assay was performed to detect neutralizing antibodies.

In clinical studies, less than 2% of patients treated with BLINCYTO tested positive for binding anti-blinatumomab antibodies. Of patients who developed anti-blinatumomab antibodies, 7 out of 9 (78%) had in vitro neutralizing activity. Anti-blinatumomab antibody formation may affect pharmacokinetics of BLINCYTO.

If formation of anti-blinatumomab antibodies with a clinically significant effect is suspected, contact Amgen at 1-800-77-AMGEN (1-800-772-6436) to discuss antibody testing.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of BLINCYTO. Because these reactions 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 drug exposure.

  • Fatal pancreatitis has been reported in patients receiving BLINCYTO in combination with dexamethasone.

DRUG INTERACTIONS

No formal drug interaction studies have been conducted with BLINCYTO. Initiation of BLINCYTO treatment causes transient release of cytokines that may suppress CYP450 enzymes. The highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the second cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index. In these patients, monitor for toxicity (e.g., warfarin) or drug concentrations (e.g., cyclosporine). Adjust the dose of the concomitant drug as needed [see CLINICAL PHARMACOLOGY].

Read the entire FDA prescribing information for Blincyto (Blinatumomab for Injection)

© Blincyto Patient Information is supplied by Cerner Multum, Inc. and Blincyto Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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