Version July 2025
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, including immune effector cell-associated neurotoxicity syndrome (ICANS), which may be severe, life-threatening, or fatal, occurred in patients receiving blinatumomab. Interrupt or discontinue blinatumomab as recommended.
Dosage guidance:
Safety: Premedication is required. Administer measures to prevent tumor lysis syndrome (eg, pretreatment nontoxic cytoreduction and hydration during treatment). Do not flush infusion line, particularly when changing infusion bags or at completion of infusion; may result in overdose. If utilizing a catheter system, before flushing the catheter system, residual blinatumomab must be aspirated to avoid bolus administration.
Clinical considerations : Intrathecal chemotherapy prophylaxis is recommended prior to and during blinatumomab treatment to prevent CNS acute lymphoblastic leukemia relapse. 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 (Ref).
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 re-initiation (eg, if treatment is interrupted for ≥4 hours).
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 (Ref).
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 (Ref).
Acute lymphoblastic leukemia, CD19 positive, B-cell precursor, Philadelphia chromosome negative, in consolidation phase: A single cycle in consolidation consists of 28 days of continuous infusion followed by a 2-week treatment-free interval (each cycle is 42 days). Blinatumomab is administered in consolidation cycles 1 and 2, followed by 3 cycles of consolidation chemotherapy, then a blinatumomab cycle, then another consolidation chemotherapy cycle, and then a fourth blinatumomab cycle (total of 8 cycles of consolidation therapy, 4 of which are blinatumomab). In the clinical study, patients could proceed to transplant after 1 to 2 cycles of blinatumomab and up to 2 cycles of consolidation chemotherapy (Ref).
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 all subsequent cycle initiations or for therapy reinitiation (eg, if treatment is interrupted for 4 or more hours).
Premedicate with dexamethasone 20 mg IV within 1 hour prior to the first dose of each blinatumomab cycle.
Patients ≥45 kg (fixed dose): Cycles 1, 2, 6, and 8: IV: 28 mcg/day administered as a continuous infusion on days 1 to 28 of a 42-day treatment cycle (Ref).
Patients <45 kg (dose based on BSA): Cycles 1, 2, 6, and 8: IV: 15 mcg/m2/day (maximum: 28 mcg/day) administered as a continuous infusion on days 1 to 28 day of a 42-day treatment cycle.
Acute lymphoblastic leukemia, CD19 positive, B-cell precursor, relapsed or 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 clinical studies, if appropriate, patients could proceed to transplant at any time after cycle 1 (Ref).
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, if treatment is interrupted for 4 or more hours).
Premedicate with dexamethasone 20 mg IV or orally 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 (Ref).
Cycles 2 through 5: IV: 28 mcg daily administered as a continuous infusion on days 1 to 28 of a 6-week treatment cycle (Ref).
Cycles 6 through 9: IV: 28 mcg daily administered as a continuous infusion on days 1 to 28 of a 12-week treatment cycle (Ref).
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 within the range observed in patients with normal kidney 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).
Hepatic function impairment at baseline:
Mild (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 times ULN and any AST) or moderate (total bilirubin >1.5 to 3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant difference in blinatumomab pharmacokinetics was observed based on mild or moderate hepatic impairment.
Severe impairment (total bilirubin >3 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Acute hepatotoxicity during treatment: Interrupt therapy if transaminases are >5 times ULN or if total bilirubin is >3 times ULN.
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 (Ref).
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.
|
Adverse reaction |
Severity |
Patients ≥45 kg |
Patients <45 kg |
|---|---|---|---|
|
a CRS = Cytokine release syndrome; 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). b ICANS = Immune effector cell-associated neurotoxicity syndrome. | |||
|
CRSa |
Grade 3 |
Interrupt blinatumomab therapy. Administer dexamethasone 8 mg IV or orally every 8 hours for up to 3 days, then taper over 4 days. When CRS is resolved, resume blinatumomab at 9 mcg/day and escalate to 28 mcg/day after 7 days if the adverse reaction does not recur. |
Interrupt blinatumomab therapy. Administer dexamethasone 5 mg/m2 (maximum: 8 mg) IV or orally every 8 hours for up to 3 days, then taper over 4 days. When CRS is resolved, resume blinatumomab at 5 mcg /m2/day and escalate to 15 mcg/m2/day after 7 days if the adverse reaction does not recur. |
|
Grade 4 |
Discontinue blinatumomab permanently. Administer dexamethasone as instructed for grade 3 CRS. | ||
|
Neurologic toxicity |
Grade 2 ICANSb |
Interrupt blinatumomab therapy. Administer corticosteroids and manage per current practice guidelines. When ICANS is resolved, resume blinatumomab at 9 mcg/day and escalate to 28 mcg/day after 7 days if the adverse reaction does not recur. |
Interrupt blinatumomab therapy. Administer corticosteroids and manage per current practice guidelines. When ICANS is resolved, resume blinatumomab at 5 mcg/m2/day and escalate to 15 mcg/m2/day after 7 days if the adverse reaction does not recur. |
|
Grade 3 (including ICANS) |
Interrupt blinatumomab until ≤ grade 1 (mild) for at least 3 days and then resume dosing at 9 mcg/day. Escalate dose to 28 mcg/day after 7 days if the adverse reaction does not recur. If adverse reaction occurred at the 9 mcg/day dose or if the adverse reaction takes >7 days to resolve, discontinue blinatumomab permanently. If ICANS, administer corticosteroids and manage per current practice guidelines. |
Interrupt blinatumomab until ≤ grade 1 (mild) for at least 3 days and then resume dosing at 5 mcg /m2/day. Escalate dose to 15 mcg /m2/day after 7 days if the adverse reaction does not recur. If adverse reaction occurred at the 5 mcg /m2/day dose or if the adverse reaction takes >7 days to resolve, discontinue blinatumomab permanently. If ICANS, administer corticosteroids and manage per current practice guidelines. | |
|
Grade 4 (including ICANS) |
Discontinue blinatumomab permanently. If ICANS, administer corticosteroids and manage per current practice guidelines. | ||
|
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 until ≤ grade 1 (mild) and then resume dosing at 9 mcg/day. Escalate dose to 28 mcg/day after 7 days if the adverse reaction does not recur. If the adverse reaction takes >14 days to resolve, discontinue blinatumomab permanently. |
Interrupt blinatumomab until ≤ grade 1 (mild) and then resume dosing at 5 mcg /m2/day. Escalate dose to 15 mcg /m2/day after 7 days if the adverse reaction does not recur. If the adverse reaction takes >14 days to resolve, discontinue blinatumomab permanently. |
|
Grade 4 |
Consider discontinuing blinatumomab permanently. | ||
Refer to adult dosing.
(For additional information see "Blinatumomab: Pediatric drug information")
Acute lymphoblastic leukemia; infant, newly diagnosed, CD19 positive B-cell precursor KMT2A rearranged: Limited data available:
Infants: IV: 15 mcg/m2/day as a continuous infusion for 4 weeks beginning after completion of a 4-week induction with the Interfant 06 regimen. In the trial, patients were premedicated with dexamethasone (5 mg/m2) administered 30 minutes prior to start of blinatumomab infusion (Ref).
Acute lymphoblastic leukemia, CD19 positive, B-cell precursor, minimal residual disease positive (≥0.1%):
Infants, Children, and Adolescents:
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 IV or oral 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); use in combination with intrathecal chemotherapy prophylaxis.
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 14-day 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 14-day 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 14-day treatment-free interval.
Consolidation: Cycles 2 to 4: Days 1 to 28: IV: 28 mcg daily administered as a continuous infusion followed by a 14-day treatment-free interval.
Acute lymphoblastic leukemia, CD19 positive, B-cell precursor, Philadelphia chromosome negative, in consolidation phase:
Infants, Children, and Adolescents:
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. Use in combination with intrathecal chemotherapy prophylaxis.
Premedicate with dexamethasone IV or oral 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.
Patient weight <45 kg: BSA-directed dosing: Consolidation: Single cycle: Days 1 to 28: IV: 15 mcg/m2/day (maximum daily dose: 28 mcg/day) administered as a continuous IV infusion followed by a 14-day treatment-free interval (Days 29 to 42).
Patient weight ≥45 kg: Fixed dosing: Consolidation: Single cycle: Days 1 to 28: IV: 28 mcg daily administered as a continuous IV infusion followed by a 14-day treatment-free interval (Days 29 to 42).
Acute lymphoblastic leukemia, CD19 positive, B-cell precursor, relapsed or 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 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 IV or oral 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); use in combination with intrathecal chemotherapy prophylaxis.
Patient weight <45 kg: BSA-directed dosing:
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 14-day 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 14-day 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 14-day 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 a 56-day 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 14-day treatment-free interval.
Cycle 2: Days 1 to 28: IV: 28 mcg daily administered as a continuous infusion followed by a 14-day treatment-free interval.
Consolidation: Cycles 3 through 5: Days 1 to 28: IV: 28 mcg daily administered as a continuous infusion followed by a 14-day treatment-free interval.
Continued therapy: Cycles 6 through 9: Days 1 to 28: IV: 28 mcg daily administered as a continuous infusion followed by a 56-day 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 2 immune effector cell-associated neurotoxicity syndrome (ICANS): Interrupt therapy and administer corticosteroids and manage per current practice guidelines. When ICANS resolves, 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 28 mcg/day if ≥45 kg.
Grade 3 (including ICANS): 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. If ICANS, administer corticosteroids and manage per current practice guidelines.
Grade 4 (including ICANS): Discontinue permanently. If ICANS, administer corticosteroids and manage per current practice guidelines.
Seizure: Discontinue permanently if more than 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 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.
Infants, Children, and Adolescents:
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).
Infants, Children, and Adolescents:
Baseline hepatic impairment: IV:
Mild (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 times ULN and any AST) or moderate (total bilirubin >1.5 to 3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant difference in blinatumomab pharmacokinetics was observed based on mild or moderate hepatic impairment.
Severe impairment (total bilirubin >3 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatotoxicity during treatment: IV: Interrupt therapy if transaminases are >5 times ULN or if bilirubin is >3 times ULN.
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: infants, children, adolescents: 26%; adults: 8%), hypotension (14%)
Dermatologic: Skin rash (12% to 16%)
Endocrine & metabolic: Weight gain (infants, children, adolescents: 17%; adults: 6% to 10%)
Hematologic & oncologic: Anemia (infants, children, adolescents: 41%; adults: 24% to 25%; grades ≥3: 19%), decreased absolute lymphocyte count (grades 3/4: 80%), decreased serum immunoglobulins (18%; including IgA, IgG, IgM, hypogammaglobulinemia; grades ≥3: 5%), leukopenia (infants, children, adolescents: 24%; adults: 8% to 14%; grades ≥3: 7% to 9%), neutropenia (15% to 31%; grades ≥3: 15% to 28%), thrombocytopenia (infants, children, adolescents: 34%; adults: 10% to 21%; grades ≥3: 6% to 18%)
Hepatic: Increased serum transaminases (9% to 15%; including increased serum alanine aminotransferase, increased serum aspartate aminotransferase)
Hypersensitivity: Cytokine release syndrome (7% to 15%), infusion-related reaction (infants, children, adolescents, adults: 30% to 77%)
Infection: Infection (28% to 39%; bacterial infection [14%], fungal infection [10%], staphylococcal infection [≥2%], viral infection [11%]), serious infection (≤25%; including bacteremia, opportunistic infection, pneumonia, sepsis)
Nervous system: Aphasia (12%), chills (28%), insomnia (18%), neurotoxicity (65%; including ataxia, balance impairment, confusion, cranial nerve disorder [facial nerve disorder, facial paresis, sixth nerve palsy, trigeminal nerve disorder, trigeminal neuralgia], disorientation, encephalopathy [10%], headache [23% to 39%], immune effector cell-associated neurotoxicity syndrome [ICANS]: 8%, impaired consciousness, seizure [≥2%; including tonic-clonic seizure], speech disturbance, tremor [31%; including essential tremor, intention tremor, resting tremor])
Neuromuscular & skeletal: Back pain (12%)
Respiratory: Cough (13%)
Miscellaneous: Fever (infants, children, adolescents, adults: 55% to 91%)
1% to 10%:
Hematologic & oncologic: Febrile neutropenia (≥2%), lymphocytopenia (≥2%)
Immunologic: Antibody development (<2%; most were neutralizing)
Infection: Septic shock (≥2%)
Nervous system: Dizziness (10%)
Frequency not defined:
Cardiovascular: Capillary leak syndrome, chest discomfort, chest pain, circulatory shock, flushing (including hot flash), peripheral edema
Dermatologic: Allergic dermatitis, erythema multiforme, fixed drug eruption, urticaria
Endocrine & metabolic: Hypovolemic shock
Hematologic & oncologic: Hemophagocytic lymphohistiocytosis, leukocytosis, lymphadenopathy, tumor lysis syndrome
Hepatic: Hyperbilirubinemia, increased serum alkaline phosphatase
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis, angioedema)
Infection: Systemic inflammatory response syndrome
Nervous system: Altered mental status, cognitive dysfunction, depressed mood, depression, disturbance in attention, drowsiness, hyperthermia, hypoesthesia, lethargy, leukoencephalopathy, memory impairment, noncardiac chest pain, pain, paresthesia, stupor, suicidal ideation
Neuromuscular & skeletal: Limb pain, musculoskeletal chest pain, ostealgia
Respiratory: Asthma, bronchospasm, dyspnea (including 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 with blinatumomab. 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 report signs/symptoms suggestive of CRS. The median time to onset of CRS was 2 days (following the start of infusion) and median time to resolution was 5 days (among cases that resolved). 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).
• 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). The clinical significance of the imaging changes is unknown.
• Neurotoxicity: Neurological toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS), which may be severe or life-threatening, have occurred. Neurotoxicity 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. The incidence of ICANS was 7.5% in clinical trials; onset may be concurrent with CRS, following resolution of CRS, or in the absence of CRS. 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. 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. Patients with Down syndrome >10 years of age may have a higher risk of seizures with blinatumomab treatment. 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 clinical trials and the postmarketing setting.
• Tumor lysis syndrome: Life-threatening or fatal tumor lysis syndrome (TLS) has been observed. 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: Patients ≥65 years of age experienced an increased rate of neurotoxicity (including cognitive disorder, encephalopathy, and 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 (use preservative-free diluents if possible) or use dosage forms containing benzyl alcohol with caution in neonates. The 72-hour and 96-hour blinatumomab infusions prepared with preservative contain 2.5 mg/mL benzyl alcohol; the 7-day blinatumomab infusion prepared with preservative contains 7.4 mg/mL benzyl alcohol. See manufacturer's labeling.
• 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. If utilizing a catheter system, before flushing the catheter system, residual blinatumomab must be aspirated to avoid bolus administration. 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.
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 [preservative free]:
Blincyto: 35 mcg (1 ea) [contains polysorbate 80]
No
Solution (reconstituted) (Blincyto Intravenous)
35 mcg (per each): $6,668.12
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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]
Note: Preparation and administration errors have occurred; carefully follow administration instructions. IV tubing should be primed with final prepared solution for infusion and not with NS. Do not flush infusion line, particularly when changing infusion bags or at completion of infusion; may result in excess dosage and complications. If utilizing a catheter system, before flushing the catheter system, residual blinatumomab must be aspirated to avoid bolus administration.
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.
72- hour infusion: Administer 130 mL as a continuous IV infusion at a constant flow rate of 1.8 mL/hour for 72 hours through a dedicated lumen. Use a programmable, lockable, non-elastomeric infusion pump with an alarm. Do not use an in-line filter for the 72-hour infusion bag.
96-hour infusion: Administer 173 mL as a continuous IV infusion at a constant flow rate of 1.8 mL/hour for 96 hours through a dedicated lumen. Use a programmable, lockable, non-elastomeric infusion pump with an alarm. Do not use an in-line filter for the 96-hour infusion bag.
7-day infusion : 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 (DEHP) PVC, or ethyl vinyl acetate infusion bags, pump cassettes, and IV tubing. 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 infuse other medications through the same line.
Note: Preparation and administration errors have occurred; carefully follow administration instructions. Do not flush infusion line, particularly when changing infusion bags or at completion of infusion; may result in excess dosage and complications. If utilizing a catheter system, before flushing the catheter system, residual blinatumomab must be aspirated to avoid bolus administration.
Parenteral: IV infusion: Infusion duration varies.
In patients <5.4 kg, do NOT administer the blinatumomab 72-hour, 96-hour, or 7-day infusion due to quantity of benzyl alcohol exposure.
Prior to infusion:
24- or 48-hour infusion: Attach the IV tubing (use only polyolefin, non-DEHP polyvinyl chloride [PVC], or ethyl vinyl acetate [EVA] tubing) to the bag with a sterile, nonpyrogenic, low protein-binding 0.2 micron in-line filter. Prime the IV tubing only with the prepared infusion solution; do not prime with NS.
72-hour, 96-hour, or 7-day infusion: 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 72-hour, 96-hour, or 7-day infusion. Prime the IV tubing only with the prepared infusion solution; do not prime with NS.
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. Discard unused infusion solution after completion of infusion.
24- or 48-hour infusion: Administer 240 mL as a continuous IV infusion at a constant flow; rate dependent on infusion duration; for 24-hour infusion, infuse at 10 mL/hour; for 48-hour infusion, infuse at 5 mL/hour 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).
72-hour infusion: Patients weighing ≥5.4 kg: Administer 130 mL as a continuous IV infusion at a constant flow rate of 1.8 mL/hour for 72 hours through a dedicated lumen. Use a programmable, lockable, nonelastomeric infusion pump with an alarm. Do not use an in-line filter for the 72-hour infusion bag. Infusion bag contains overfill (to account for tubing priming volume).
96-hour infusion: Patients weighing ≥5.4 kg: Administer 173 mL as a continuous IV infusion at a constant flow rate of 1.8 mL/hour for 96 hours through a dedicated lumen. Use a programmable, lockable, nonelastomeric infusion pump with an alarm. Do not use an in-line filter for the 96-hour infusion bag. Infusion bag contains overfill (to account for tubing priming volume).
7-day infusion: Patients weighing ≥5.4 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).
Hazardous agent (NIOSH 2024 [table 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
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/2023/125557s023s026lbl.pdf#page=41
Acute lymphoblastic leukemia, CD19-positive, minimal residual disease-positive: Treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) ≥0.1% in adults and pediatric patients ≥1 month of age.
Acute lymphoblastic leukemia, CD19 positive, Philadelphia chromosome negative, in consolidation phase: Treatment of CD19 positive, Philadelphia chromosome negative B-cell precursor ALL in the consolidation phase of multiphase chemotherapy in adults and pediatric patients ≥1 month of age.
Acute lymphoblastic leukemia, CD19-positive, relapsed or refractory: Treatment of relapsed or refractory CD19-positive B-cell precursor ALL in adults and pediatric patients ≥1 month of age.
Blinatumomab may be confused with bezlotoxumab, obinutuzumab.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
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.
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Busulfan: Blinatumomab may increase serum concentration of Busulfan. Risk C: Monitor
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. 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 (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects 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 decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects 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 decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects 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 increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects 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 increase immunosuppressive effects 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
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of 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 increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects 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
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects 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
Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects 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 Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects 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
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status prior to initiating treatment in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for 48 hours after the last blinatumomab dose.
Based on the mechanism of action, in utero exposure to blinatumomab may cause fetal harm. Pregnancy may be compromised due to activation of the maternal immune system. In addition, newborns exposed to blinatumomab 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, neurotoxicity (including immune effector cell-associated neurotoxicity syndrome [ICANS]), infusion reactions, 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: 5.27 L.
Metabolism: Degraded into small peptides and amino acids via catabolic pathways.
Half-life elimination: Pediatric patients <18 years of age: 2.04 ± 1.35 hours; Adults: 2.2 hours.
Excretion: Urine (negligible amounts).
Clearance: Mean systemic clearance: Adults: 3.1 L/hour.
Body surface area: BSA (0.4 to 2.9 m2) influences blinatumomab pharmacokinetics, supporting BSA-based dosing for patients weighing <45 kg.
