Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving blinatumomab. Interrupt or discontinue blinatumomab and treat with corticosteroids as recommended.
Neurological toxicities, which may be severe, life-threatening, or fatal, occurred in patients receiving blinatumomab. Interrupt or discontinue blinatumomab as recommended.
Note: Administer measures to prevent tumor lysis syndrome (eg, pretreatment nontoxic cytoreduction and hydration during treatment). Consider prophylactic antibiotics to prevent infection if appropriate; manage promptly if infection occurs.
Acute lymphoblastic leukemia, CD19-positive B-cell precursor, minimal residual disease–positive (≥0.1%): Each induction or consolidation treatment cycle consists of 4 weeks of continuous infusion followed by a 2-week treatment-free interval (allow at least 2 weeks treatment-free between cycles). Therapy involves 1 induction cycle followed by up to 3 additional cycles for consolidation (total of up to 4 cycles). In the clinical study, patients could proceed to transplant at any time after cycle 1 (Gökbuget 2018).
Note: Hospitalization is recommended for the first 3 days of cycle 1, and the first 2 days of cycle 2. Close observation by a health care professional (or hospitalization) is recommended for initiation of all subsequent cycles or for therapy reinitiation (eg, treatment is interrupted for 4 or more hours). Do not flush infusion line, particularly when changing infusion bags or at completion of infusion; may result in overdose.
Premedicate with the IV equivalent to prednisone 100 mg or dexamethasone 16 mg IV one hour prior to the first dose of each cycle.
Patients ≥45 kg (fixed dose): Cycles 1 to 4: IV: 28 mcg daily administered as a continuous infusion on days 1 to 28 of a 6-week treatment cycle (Gökbuget 2018).
Patients <45 kg (dose based on BSA): Cycles 1 to 4: IV: 15 mcg/m2/day (maximum: 28 mcg/day) as a continuous infusion on days 1 to 28 of a 6-week treatment cycle (Gökbuget 2018).
Acute lymphoblastic leukemia, CD19-positive B-cell precursor, relapsed/refractory: Each induction or consolidation treatment cycle consists of 4 weeks of continuous infusion followed by a 2-week treatment-free interval (allow at least 2 weeks treatment-free between cycles). Each continued therapy cycle consists of 4 weeks of continuous infusion followed by an 8-week treatment-free interval. Therapy involves up to 2 induction cycles followed by 3 additional cycles for consolidation and up to 4 additional cycles of continued therapy (total of up to 9 cycles). In the clinical study, if appropriate, patients could proceed to transplant at any time after cycle 1 (Kantarjian 2017).
Note: Hospitalization is recommended for the first 9 days of cycle 1, and the first 2 days of cycle 2. Close observation by a health care professional (or hospitalization) is recommended for initiation of all subsequent cycles or for therapy reinitiation (eg, treatment is interrupted for 4 or more hours). Do not flush infusion line, particularly when changing infusion bags or at completion of infusion; may result in overdose.
Premedicate with dexamethasone 20 mg one hour prior to the first dose of each cycle, prior to a step dose (eg, Cycle 1 day 8), and when restarting therapy after an interruption of ≥4 hours.
Patients ≥45 kg (fixed dose):
Cycle 1: IV: 9 mcg daily administered as a continuous infusion on days 1 to 7, followed by 28 mcg daily as a continuous infusion on days 8 to 28 of a 6-week treatment cycle (Kantarjian 2017).
Cycles 2 through 5: IV: 28 mcg daily administered as a continuous infusion on days 1 to 28 of a 6-week treatment cycle (Kantarjian 2017).
Cycles 6 through 9: IV: 28 mcg daily administered as a continuous infusion on days 1 to 28 of a 12-week treatment cycle (Kantarjian 2017).
Patients <45 kg (dose based on BSA):
Cycle 1: IV: 5 mcg/m2/day (maximum: 9 mcg/day) administered as a continuous infusion on days 1 to 7, followed by 15 mcg/m2/day (maximum: 28 mcg/day) as a continuous infusion on days 8 to 28 of a 6-week treatment cycle.
Cycles 2 through 5: IV: 15 mcg/m2/day (maximum: 28 mcg/day) administered as a continuous infusion on days 1 to 28 of a 6-week treatment cycle.
Cycles 6 through 9: IV: 15 mcg/m2/day (maximum: 28 mcg/day) administered as a continuous infusion on days 1 to 28 of a 12-week treatment cycle.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, a pharmacokinetic analysis showed that clearance values in patients with CrCl 30 to 59 mL/minute were similar to the range observed in patients with normal renal function.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatotoxicity during treatment: Interrupt therapy if transaminases are >5 times ULN or if bilirubin is >3 times ULN.
(For additional information see "Blinatumomab: Pediatric drug information")
Acute lymphoblastic leukemia (CD19-positive B-cell precursor), MRD-positive (≥0.1%): Children and Adolescents: Note: Use in infants may be directed within certain investigational protocols; refer to specific protocols for additional information.
Note: Hospitalization is recommended for the first 3 days of cycle 1 and the first 2 days of cycle 2. Close observation by a health care professional (or hospitalization) is recommended for initiation of all subsequent cycles or for therapy reinitiation (eg, treatment is interrupted for 4 or more hours). Do not flush infusion line, particularly when changing infusion bags or at completion of infusion; may result in overdose.
Premedicate with dexamethasone 5 mg/m2 (maximum dose: 20 mg/dose) 1 hour prior to the first dose of the first cycle, or when restarting therapy after an interruption of ≥4 hours in the first cycle.
Blinatumomab treatment course involves 1 induction cycle followed by up to 3 additional cycles for consolidation (total of up to 4 cycles).
Patient weight <45 kg: BSA-directed dosing:
Induction: Cycle 1: Days 1 to 28: IV: 15 mcg/m2/day (maximum daily dose: 28 mcg/day) administered as a continuous infusion followed by a 2-week treatment-free interval.
Consolidation: Cycles 2 to 4: Days 1 to 28: IV: 15 mcg/m2/day (maximum daily dose: 28 mcg/day) administered as a continuous infusion followed by a 2-week treatment-free interval.
Patient weight ≥45 kg: Fixed dosing:
Induction: Cycle 1: Days 1 to 28: IV: 28 mcg daily administered as a continuous infusion followed by a 2-week treatment-free interval.
Consolidation: Cycles 2 to 4: Days 1 to 28: IV: 28 mcg daily administered as a continuous infusion followed by a 2-week treatment-free interval.
Acute lymphoblastic leukemia (CD19-positive B-cell precursor), relapsed/refractory: Infants, Children, and Adolescents:
Note: Hospitalization is recommended for the first 9 days of cycle 1, and the first 2 days of cycle 2. Close observation by a healthcare professional (or hospitalization) is recommended for initiation of all subsequent cycles or for therapy reinitiation (eg, treatment is interrupted for 4 or more hours). Do not flush infusion line, particularly when changing infusion bags or at completion of infusion; may result in overdose.
Premedicate with dexamethasone IV 5 mg/m2 (maximum dose: 20 mg/dose) 1 hour prior to the first dose of the first cycle, prior to a step dose (eg, Cycle 1 day 8), or when restarting therapy after an interruption of ≥4 hours in the first cycle.
Blinatumomab treatment course involves 2 induction cycles followed by 3 additional cycles for consolidation and up to 4 additional cycles of continued therapy (total of up to 9 cycles).
Patient weight <45 kg: BSA-directed:
Induction:
Cycle 1:
Days 1 to 7: IV: 5 mcg/m2/day (maximum daily dose: 9 mcg/day) administered as a continuous infusion.
Days 8 to 28: IV: 15 mcg/m2/day (maximum daily dose: 28 mcg/day) administered as a continuous infusion followed by a 2-week treatment-free interval.
Cycle 2: Days 1 to 28: IV: 15 mcg/m2/day (maximum daily dose: 28 mcg/day) administered as a continuous infusion followed by a 2-week treatment-free interval.
Consolidation: Cycles 3 through 5: Days 1 to 28: IV: 15 mcg/m2/day (maximum daily dose: 28 mcg/day) administered as a continuous infusion followed by a 2-week treatment-free interval.
Continued therapy: Cycles 6 through 9: Days 1 to 28: IV: 15 mcg/m2/day (maximum daily dose: 28 mcg/day) administered as a continuous infusion followed by 8-week treatment-free interval.
Patient weight ≥45 kg: Fixed dosing:
Induction:
Cycle 1:
Days 1 to 7: IV: 9 mcg daily administered as a continuous infusion.
Days 8 to 28: IV: 28 mcg daily administered as a continuous infusion followed by a 2-week treatment-free interval.
Cycle 2: Days 1 to 28: IV: 28 mcg daily administered as a continuous infusion followed by a 2-week treatment-free interval.
Consolidation: Cycles 3 through 5: Days 1 to 28: IV: 28 mcg daily administered as a continuous infusion followed by a 2-week treatment-free interval.
Continued therapy: Cycles 6 through 9: Days 1 to 28: IV: 28 mcg daily administered as a continuous infusion followed by an 8-week treatment-free interval.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Infants, Children, and Adolescents: If the interruption after an adverse reaction is no longer than 7 days, continue the same cycle to a total of 28 days of infusion inclusive of the days before and after the interruption in that cycle. If an interruption due to an adverse reaction is longer than 7 days, start a new cycle.
Cytokine release syndrome (CRS):
Grade 3: Interrupt blinatumomab therapy, administer dexamethasone according to the following; and upon resolution, resume blinatumomab at the following reduced doses:
Dexamethasone: IV, Oral:
Patient weight <45 kg: 5 mg/m2/dose (maximum dose: 8 mg/dose) every 8 hours for up to 3 days, then taper over 4 days.
Patient weight ≥45 kg: 8 mg/dose every 8 hours for up to 3 days, then taper over 4 days.
Blinatumomab: After resolution, resume therapy at the following reduced doses:
Patient weight <45 kg: 5 mcg/m2/day (maximum daily dose: 9 mcg/day); if after 7 days adverse reaction does not recur, further increase dose to 15 mcg/m2/day (maximum daily dose: 28 mcg/day).
Patient weight ≥45 kg: 9 mcg/day. If after 7 days adverse reaction does not recur, further increase dose to 28 mcg/day.
Grade 4: Discontinue blinatumomab permanently, administer dexamethasone according to the following:
Dexamethasone: IV, Oral:
Patient weight <45 kg: 5 mg/m2/dose (maximum dose: 8 mg/dose) every 8 hours for up to 3 days, then taper over 4 days.
Patient weight ≥45 kg: 8 mg/dose every 8 hours for up to 3 days, then taper over 4 days.
Neurologic toxicity:
Grade 3: Interrupt therapy for at least 3 days and until toxicity is ≤ Grade 1 (mild), then resume blinatumomab dosing at 5 mcg/m2/day if <45 kg (maximum daily dose: 9 mcg/day) or 9 mcg/day if ≥45 kg. If after 7 days adverse reaction does not recur, further increase blinatumomab dose to 15 mcg/m2/day if <45 kg (maximum daily dose: 28 mcg/day) or to 28 mcg/day if ≥45 kg. If adverse reaction occurred at the 5 mcg/m2/day dose (if <45 kg) or 9 mcg daily dose, or if it takes more than 7 days to resolve, discontinue permanently.
Grade 4: Discontinue permanently.
Seizure: Discontinue permanently if more than 1 seizure occurs.
Other clinically relevant toxicity:
Grade 3: Interrupt therapy until adverse reaction is ≤ Grade 1 (mild), then restart blinatumomab dosing at 5 mcg/m2/day if <45 kg (maximum daily dose: 9 mcg/day) or 9 mcg/day if ≥45 kg. If after 7 days adverse reaction does not recur, further increase blinatumomab dose to 15 mcg/m2/day if <45 kg (maximum daily dose: 28 mcg/day) or to 28 mcg/day if ≥45 kg. If adverse reaction takes more than 14 days to resolve, discontinue permanently.
Grade 4: Consider discontinuing permanently.
All patients:
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, a pharmacokinetic analysis showed that clearance values in patients with CrCl 30 to 59 mL/minute were similar to the range observed in patients with normal renal function.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
All patients:
Baseline hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatotoxicity during treatment: Interrupt therapy if transaminases are >5 times ULN or if bilirubin is >3 times ULN
Refer to adult dosing.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: The dosing in the FDA-approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m2 experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status. If dose reduction for toxicity is recommended in the prescribing information, the dose should be increased back to the initial or previously tolerated dose only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (ASCO [Griggs 2021]).
If the interruption after an adverse reaction is ≤7 days, continue the same cycle to a total of 28 days of infusion inclusive of days before and after the interruption in that cycle. If an interruption due to an adverse reaction is >7 days, start a new cycle.
Cytokine release syndrome:
Grade 3: Interrupt blinatumomab therapy. Administer dexamethasone 8 mg (or 5 mg/m2 if <45 kg; maximum: 8 mg) IV or orally every 8 hours for up to 3 days, then taper over 4 days. Upon resolution, resume blinatumomab dosing at 9 mcg daily (or 5 mcg/m2/day if <45 kg). Increase dose to 28 mcg daily (or 15 mcg/m2/day if <45 kg) after 7 days if adverse reaction does not recur.
Grade 4: Discontinue blinatumomab permanently. Administer dexamethasone 8 mg (or 5 mg/m2 if <45 kg; maximum: 8 mg) IV or orally every 8 hours for up to 3 days, then taper over 4 days.
Tocilizumab may be considered in the management of severe or life-threatening cytokine release syndrome associated with bi-specific T-cell engaging (BiTE) therapy (Lee 2014; Maude 2014).
Neurologic toxicity:
Grade 3: Interrupt blinatumomab therapy for ≥3 days and until ≤ grade 1 (mild), then resume dosing at 9 mcg daily (or 5 mcg/m2/day if <45 kg). Increase dose to 28 mcg daily (or 15 mcg/m2/day if <45 kg) after 7 days if adverse reaction does not recur. If adverse reaction occurred at the 9 mcg daily dose (or 5 mcg/m2/day dose if <45 kg), or if it takes >7 days to resolve, discontinue permanently.
Grade 4: Discontinue blinatumomab permanently.
Seizure: Discontinue blinatumomab permanently if >1 seizure occurs.
Neutropenia, prolonged: Interrupt blinatumomab treatment.
Pancreatitis: May require temporary interruption or discontinuation of blinatumomab treatment.
Tumor lysis syndrome: May require temporary interruption or discontinuation of blinatumomab treatment.
Other clinically relevant toxicity:
Grade 3: Interrupt blinatumomab therapy until ≤ grade 1 (mild), then restart at 9 mcg daily (or 5 mcg/m2/day if <45 kg). Increase dose to 28 mcg daily (or 15 mcg/m2/day if <45 kg) after 7 days if adverse reaction does not recur. If adverse reaction takes >14 days to resolve, discontinue permanently.
Grade 4: Consider discontinuing blinatumomab permanently.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Blincyto: 35 mcg (1 ea) [contains polysorbate 80]
No
Provided with IV solution stabilizer to coat the prefilled NS bag prior to addition of reconstituted blinatumomab (do NOT use IV solution stabilizer for reconstitution of blinatumomab).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Blincyto: 38.5 mcg (1 ea) [contains polysorbate 80]
An FDA-approved patient medication guide, which is available with the product and as follows, must be dispensed with this medication:
Blincyto: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125557s021lbl.pdf#page=40
Note: Preparation and administration errors have occurred; carefully follow administration instructions.
IV:
24- or 48-hour infusion: Administer 240 mL as a continuous IV infusion at a constant flow rate of 10 mL/hour for 24 hours or 5 mL/hour for 48 hours (depending on dose, duration, and/or concentration) through a dedicated lumen. Use a programmable, lockable, non-elastomeric infusion pump with an alarm. IV tubing should include a sterile, nonpyrogenic, low protein-binding, 0.2 micron in-line filter.
7-day infusion ( not recommended in patients weighing <22 kg): Administer 100 mL as a continuous IV infusion at a constant flow rate of 0.6 mL/hour for 7 days through a dedicated lumen. Use a programmable, lockable, non-elastomeric infusion pump with an alarm. Do not use an in-line filter for the 7-day infusion bag.
Only use polyolefin, non-di-ethylhexylphthalate PVC, or ethyl vinyl acetate infusion bags, pump cassettes, and IV tubing. IV tubing should be primed with final prepared solution for infusion and not with NS. Premedication is required prior to some doses (see Dosing: Adult for further details).
Infusion bag contains overfill (to account for tubing priming volume). Discard unused infusion solution after completion of infusion. Do not flush infusion line, particularly when changing infusion bags or at completion of infusion; may result in excess dosage and complications. Do not infuse other medications through the same line.
IV: Note: Preparation and administration errors have occurred; carefully follow administration instructions.
Prior to infusion: Premedication is required prior to some doses (see Dosing: Pediatric for further details).
24- or 48-hour infusion: Attach the IV tubing (use only polyolefin, non-DEHP PVC, or EVA tubing) to the bag with a sterile, non-pyrogenic, low protein-binding 0.2 micron in-line filter. Remove air from the IV bag. Prime the IV tubing only with the prepared infusion solution; do not prime with NS.
7-day infusion: Patients weighing ≥22 kg: Attach the IV tubing (use only polyolefin, non-DEHP PVC, or EVA tubing) to the bag; an in-line filter is not required for the 7-day infusion bag. Remove air from the IV bag. Prime the IV tubing only with the prepared infusion solution; do not prime with NS.
Infusion:
24- or 48-hour infusion: Administer 240 mL as a continuous IV infusion at a constant flow rate of 10 mL/hour for 24 hours or 5 mL/hour for 48 hours (depending on dose and concentration) through a dedicated lumen. Use a programmable, lockable, nonelastomeric infusion pump with an alarm. Infusion bag contains overfill (to account for tubing and priming volume). Do not flush infusion line, particularly when changing infusion bags or at completion of infusion; may result in excess dosage and complications. Do not infuse other medications through the same line. Discard unused infusion solution after completion of infusion.
7-day infusion: Patients weighing ≥22 kg: Administer 100 mL as a continuous IV infusion at a constant flow rate of 0.6 mL/hour for 7 days through a dedicated lumen. Use a programmable, lockable, nonelastomeric infusion pump with an alarm. Do not use an in-line filter for the 7-day infusion bag. Infusion bag contains overfill (to account for tubing priming volume). Do not flush infusion line, particularly when changing infusion bags or at completion of infusion; may result in excess dosage and complications. Do not infuse other medications through the same line. Discard unused infusion solution after completion of infusion.
Acute lymphoblastic leukemia, minimal residual disease–positive (CD19-positive): Treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease ≥0.1% in adults and children.
Acute lymphoblastic leukemia, relapsed or refractory (CD19-positive): Treatment of relapsed or refractory CD19-positive B-cell precursor ALL in adults and children.
Blinatumomab may be confused with belantamab mafodotin, bezlotoxumab, obinutuzumab
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
Preparation and administration errors have occurred. Do not flush infusion line, particularly when changing infusion bags or at completion of infusion; may result in overdose and complications. IV bag contains overfill and volume will be more than the volume administered to the patient to account for IV line priming and to ensure that the full dose is administered. Carefully follow preparation and administration instructions. Refer to manufacturer labeling for further information.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults unless otherwise indicated.
>10%:
Cardiovascular: Cardiac arrhythmia (12% to 14%), edema (18%), hypertension (including hypertensive crisis: adults: 8%; infants, children, adolescents: 26%), hypotension (14%)
Dermatologic: Skin rash (12% to 16%)
Endocrine & metabolic: Weight gain (adults: 6% to 10%; infants, children, adolescents: 17%)
Hematologic & oncologic: Anemia (adults: 24% to 25%; grades ≥3: 19%; infants, children, adolescents: 41%), decreased absolute lymphocyte count (grades 3/4: 80%), decreased serum immunoglobulins (18%; including IgA, IgG, IgM and hypogammaglobulinemia; grades ≥3: 5%), leukopenia (adults: 8% to 14%; grades ≥3: 7% to 9%; infants, children, adolescents: 24%), neutropenia (15% to 31%; grades ≥3: 15% to 28%), thrombocytopenia (adults: 10% to 21%; grades ≥3: 6% to 18%; infants, children, adolescents: 34%)
Hepatic: Increased serum transaminases (9% to 15%; including increased serum alanine aminotransferase, increased serum aspartate aminotransferase)
Hypersensitivity: Cytokine release syndrome (7% to 15%)
Infection: Infection (28% to 39%; bacterial infection [14%], fungal infection [10%], staphylococcal infection [≥2%], viral infection [11%]), serious infection (≤25%, including bacteremia, catheter infection, opportunistic infection, pneumonia, sepsis)
Nervous system: Aphasia (12%), chills (28%), headache (23% to 39%), insomnia (18%), neurotoxicity (65%)
Neuromuscular & skeletal: Back pain (12%), tremor (31%; including essential tremor, intention tremor, resting tremor)
Respiratory: Cough (13%)
Miscellaneous: Fever (infants, children, adolescents, and adults: 55% to 91%), infusion related reaction (infants, children, adolescents, and adults: 30% to 77%)
1% to 10%:
Cardiovascular: Septic shock (≥2%)
Hematologic & oncologic: Febrile neutropenia (≥2%), lymphocytopenia (≥2%)
Immunologic: Antibody development (<2%; most were neutralizing)
Nervous system: Dizziness (10%), encephalopathy (10%), seizure (≥2%; including tonic-clonic movements)
Frequency not defined:
Cardiovascular: Capillary leak syndrome, chest discomfort, chest pain, circulatory shock, flushing (including hot flash), peripheral edema
Dermatologic: Allergic dermatitis, erythema multiforme, urticaria
Endocrine & metabolic: Hypovolemic shock
Hematologic & oncologic: Hematologic abnormality (hematophagic histiocytosis), leukocytosis, lymphadenopathy, tumor lysis syndrome
Hepatic: Hyperbilirubinemia, increased serum alkaline phosphatase
Hypersensitivity: Anaphylaxis, angioedema, fixed drug eruption, hypersensitivity reaction
Infection: Systemic inflammatory response syndrome
Nervous system: Altered mental status, ataxia, balance impairment, cognitive dysfunction, confusion, cranial nerve disorder (including facial nerve disorder, facial paresis, sixth nerve palsy, trigeminal nerve disorder, trigeminal neuralgia), depressed mood, depression, disorientation, disturbance in attention, drowsiness, hyperthermia, hypoesthesia, impaired consciousness, lethargy, leukoencephalopathy, memory impairment, noncardiac chest pain, pain, paresthesia, speech disturbance, stupor, suicidal ideation
Neuromuscular & skeletal: Limb pain, musculoskeletal chest pain, ostealgia
Respiratory: Asthma, bronchospasm, dyspnea, dyspnea on exertion, productive cough, respiratory distress, respiratory failure (including acute respiratory failure), tachypnea, wheezing
Postmarketing: Gastrointestinal: Pancreatitis
Known hypersensitivity to blinatumomab or any component of the formulation
Concerns related to adverse effects:
• Bone marrow suppression: Neutropenia and neutropenic fever, including life-threatening episodes, have been reported; neutropenia may be prolonged.
• Cytokine release syndrome: Cytokine release syndrome (CRS), which may be life-threatening or fatal, has occurred. CRS manifestations may include pyrexia, headache, nausea, weakness, hypotension, increased transaminases, elevated total bilirubin, and disseminated intravascular coagulation. Symptoms of infusion reactions, capillary leak syndrome, and hemophagocytic histiocytosis/macrophage activation syndrome may overlap with CRS symptoms. Advise patients to reports signs/symptoms suggestive of CRS. Administer corticosteroids for severe or life-threatening CRS. The median time to onset and resolution of CRS was 2 days (following the start of infusion) and 5 days (among cases that resolved), respectively. In one study, patients with a high tumor burden (≥50% leukemic blasts or >15,000/mm3 peripheral blood leukemic blast counts), or elevated lactate dehydrogenase were pretreated with dexamethasone (10 to 24 mg/m2/day for up to 5 days and concluding 3 days prior to initiating blinatumomab) to reduce the incidence of severe CRS (Topp 2015). Tocilizumab may be considered in the management of severe or life-threatening CRS associated with bi-specific T-cell engaging (BiTE) therapy (Lee 2014; Maude 2014).
• Hepatotoxicity: Transient increases in liver enzymes (associated both with and without CRS) may occur during therapy. In patients with acute lymphoblastic leukemia (ALL), the median time to enzyme elevation was 3 to 19 days; grade 3 or higher elevations were observed in a small percentage of patients.
• Infection: Serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-related infections have been reported in approximately one-fourth of patients with ALL in clinical trials (may be life-threatening or fatal). Consider prophylactic antibiotics if appropriate. Treat promptly if infection occurs.
• Leukoencephalopathy: Leukoencephalopathy (as seen on MRI) has been reported, particularly in those patients who received prior treatment with cranial irradiation and antileukemia chemotherapy (eg, high-dose methotrexate, intrathecal cytarabine).
• Neurotoxicity: Neurological toxicities, which may be severe, life-threatening, or fatal, have occurred. Neurotoxicity has occurred in almost two-thirds of patients with ALL in clinical trials. The median time to onset was within the first 2 weeks of therapy. Common neurological symptoms include headache and tremor (symptoms may differ in children <2 years of age, and elderly patients have a higher incidence of neurotoxicity). Grade 3 or higher neurotoxicity (eg, encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders) has also been observed; other manifestations have included cranial nerve disorders. Neurotoxicity may be managed with dexamethasone (Topp 2015). Patients are at risk for loss of consciousness due to neurologic events while taking blinatumomab; advise patients to avoid driving, participating in hazardous occupations, or operating heavy or dangerous machinery during treatment. Patients with a history of (or current) clinically relevant CNS pathology were excluded from clinical trials. Advise patients to reports signs/symptoms suggestive of neurologic toxicity. The majority of symptoms resolved after interrupting therapy.
• Pancreatitis: Fatal cases of pancreatitis in patients receiving blinatumomab plus dexamethasone have been reported in the postmarketing setting.
• Tumor lysis syndrome: Life-threatening or fatal tumor lysis syndrome (TLS) has been observed. Administer measures to prevent TLS (eg, pretreatment nontoxic cytoreduction and hydration during treatment). Signs/symptoms of TLS include acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, and/or hyperphosphatemia.
Concomitant drug therapy issues:
• Vaccines: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to blinatumomab initiation, during treatment, and until immune system recovery following the last cycle of therapy.
Special populations:
• Older adult: Elderly patients experienced an increased rate of neurotoxicity (including cognitive disorder), encephalopathy, confusion, and serious infections as compared to patients <65 years of age.
• Pediatric: Pediatric patients experienced an increased rate of anemia, leukopenia, thrombocytopenia, pyrexia, infusion reaction, weight gain, and hypertension as compared to adult patients. While the incidence of neurologic toxicities in patients <2 years of age did not differ from other age groups, the manifestations were different; reported toxicities were agitation, headache, insomnia, somnolence, and irritability. Infants experienced an increased incidence of hypokalemia compared to adults and to older pediatric patients.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Diluent may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling. Due to the addition of bacteriostatic saline, the 7-day infusion bags of blinatumomab contain benzyl alcohol and are not recommended for use in patients weighing <22 kg.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Other warnings/precautions:
• Safety issue: Preparation and administration errors have occurred. Do not flush infusion line, particularly when changing infusion bags or at completion of infusion; may result in overdose and complications. IV bag contains overfill and volume will be more than the volume administered to the patient to account for IV line priming and to ensure that the full dose is administered. Follow preparation and administration instructions carefully. Refer to manufacturer labeling for further information.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Busulfan: Blinatumomab may increase the serum concentration of Busulfan. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Verify pregnancy status prior to initiating treatment in patients who could become pregnant; effective contraception should be used during treatment and for at least 48 hours after the last blinatumomab dose.
Based on the mechanism of action, blinatumomab may cause fetal harm if administered during pregnancy. Newborns exposed in utero may develop B-cell lymphocytopenia; monitor B-lymphocytes prior to administering live virus vaccines.
It is not known if blinatumomab is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for at least 48 hours after the last blinatumomab dose.
CBC with differential, liver function tests (ALT, AST, GGT, and total bilirubin) at baseline and throughout therapy. Verify pregnancy status prior to treatment initiation in patients who could become pregnant. Monitor for signs/symptoms of cytokine release syndrome, infusion reactions, neurotoxicity, infection, pancreatitis, and tumor lysis syndrome.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Blinatumomab is a bispecific T-cell engager (BiTE) which binds to CD19 expressed on B-cells and CD3 expressed on T-cells. It activates endogenous T cells by connecting CD3 in the T-cell receptor complex with CD19 on B-cells (malignant and benign), thus forming a cytolytic synapse between a cytotoxic T-cell and the cancer target B-cell (Topp 2014). Blinatumomab mediates the production of cytolytic proteins, release of inflammatory cytokines, and proliferation of T cells, which result in lysis of CD19-positive cells.
Distribution: Pediatric patients <18 years of age: 3.14 ± 2.97 L/m2; Adults: 4.35 L.
Half-life elimination: Pediatric patients <18 years of age: 2.04 ± 1.35 hours; Adults: 2.1 hours.
Excretion: Urine (negligible amounts).
Clearance: Mean systemic clearance: Adults: 3.11 L/hour.
Solution (reconstituted) (Blincyto Intravenous)
35 mcg (per each): $5,552.58
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