Blincyto (blinatumomab)

WARNING

CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

• Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving Blincyto. Interrupt or discontinue Blincyto as recommended.
• Neurological toxicities, which may be severe, life-threatening, or fatal, occurred in patients receiving Blincyto. Interrupt or discontinue Blincyto as recommended.

Common side effects of Blincyto include:

• fever
• headache
• swelling of the extremities
• nausea
• tremor
• rash
• constipation
• fever accompanying low levels of white blood cells (febrile neutropenia), and
• low levels of potassium in the blood (hypokalemia)
• anemia
• low platelet levels in the blood
• low white blood cell count
• irregular heartbeats (arrhythmia)
• diarrhea
• abdominal pain
• vomiting
• fatigue
• chills
• chest pain
• infections
• weight gain
• decreased appetite
• back pain
• pain in extremities
• bone pain
• joint pain
• dizziness
• insomnia
• cough
• shortness of breath
• nosebleeds
• high or low blood pressure (hypertension or hypotension)

Treatment Of MRD-Positive B-Cell Precursor ALL

• A treatment course consists of 1 cycle of Blincyto for induction followed by up to 3 additional cycles for consolidation.
• A single cycle of treatment of Blincyto induction or consolidation consists of 28 days of continuous intravenous infusion followed by a 14-day treatment-free interval (total 42 days).
• See Table 1 for the recommended dose by patient weight and schedule. Patients weighing 45 kg or more receive a fixed-dose. For patients weighing less than 45 kg, the dose is calculated using the patient’s body surface area (BSA).

Table 1. Recommended Blincyto Dose and Schedule for the Treatment of MRD-positive B-cell Precursor ALL

• Hospitalization is recommended for the first 3 days of the first cycle and the first 2 days of the second cycle. For all subsequent cycle starts and re-initiations (e.g., if treatment is interrupted for 4 or more hours), supervision by a healthcare professional or hospitalization is recommended.
• Premedicate with prednisone or equivalent for MRD-positive B-cell Precursor ALL
  • For adult patients, premedicate with prednisone 100 mg intravenously or equivalent (e.g., dexamethasone 16 mg) 1 hour prior to the first dose of Blincyto in each cycle.
  • For pediatric patients, premedicate with 5 mg/m² of dexamethasone, to a maximum dose of 20 mg, prior to the first dose of Blincyto in the first cycle and when restarting an infusion after an interruption of 4 or more hours in the first cycle.
• For administration of Blincyto:
  • See Section 2.5 for infusion over 24 hours or 48 hours.
  • See Section 2.6 for infusion over 7 days using Bacteriostatic 0.9% Sodium Chloride Injection, USP (containing 0.9% benzyl alcohol). This option is available for patients weighing 22 kg or more. It is not recommended for use in patients weighing less than 22 kg.

Treatment Of Relapsed Or Refractory B-Cell Precursor ALL

• A treatment course consists of up to 2 cycles of Blincyto for induction followed by 3 additional cycles for consolidation and up to 4 additional cycles of continued therapy.
• A single cycle of treatment of Blincyto induction or consolidation consists of 28 days of continuous intravenous infusion followed by a 14-day treatment-free interval (total 42 days).
• A single cycle of treatment of Blincyto continued therapy consists of 28 days of continuous intravenous infusion followed by a 56-day treatment-free interval (total 84 days).
• See Table 2 for the recommended dose by patient weight and schedule. Patients weighing 45 kg or more receive a fixed-dose and for patients weighing less than 45 kg, the dose is calculated using the patient’s BSA.

Table 2. Recommended Blincyto Dose and Schedule for the Treatment of Relapsed or Refractory B-cell Precursor ALL

• Hospitalization is recommended for the first 9 days of the first cycle and the first 2 days of the second cycle. For all subsequent cycle starts and re-initiation (e.g., if treatment is interrupted for 4 or more hours), supervision by a healthcare professional or hospitalization is recommended.
• Premedicate with dexamethasone:
  • For adult patients, premedicate with 20 mg of dexamethasone 1 hour prior to the first dose of Blincyto of each cycle, prior to a step dose (such as Cycle 1 Day 8), and when restarting an infusion after an interruption of 4 or more hours.
  • For pediatric patients, premedicate with 5 mg/m² of dexamethasone, to a maximum dose of 20 mg, prior to the first dose of Blincyto in the first cycle, prior to a step dose (such as Cycle 1 Day 8), and when restarting an infusion after an interruption of 4 or more hours in the first cycle.
• For administration of Blincyto:
  • See Section 2.5 for infusion over 24 hours or 48 hours.
  • See Section 2.6 for infusion over 7 days using Bacteriostatic 0.9% Sodium Chloride Injection, USP (containing 0.9% benzyl alcohol). This option is available for patients weighing 22 kg or more. It is not recommended for use in patients weighing less than 22 kg.

Dosage Modifications For Adverse Reactions

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 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.

Table 3. Dosage Modifications for Adverse Reactions

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

• Based on its mechanism of action, Blincyto may cause fetal harm, including B-cell lymphocytopenia, when administered to a pregnant woman.
• There are no data on the use of Blincyto in pregnant women.
• There is no information regarding the presence of blinatumomab in human milk, the effects on the breastfed infant, or the effects on milk production.
• Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in breastfed infants from Blincyto, including B-cell lymphocytopenia, advise patients not to breastfeed during treatment with Blincyto and for at least 48 hours after the last dose.