Blinatumomab

What is Blinatumomab?

Blinatumomab

• Blinatumomab (Blincyto) is a bispecific CD19-directed CD3 T-cell engager used for the treatment of B-cell precursor acute lymphoblastic leukemia (ALL).

What are the uses of this medicine?

This medicine is used to treat adults and children with:

• CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in remission with molecular evidence of leukemia
• CD19-positive B-cell precursor ALL that has come back or did not respond to previous treatments

How does this medicine work?

• Blinatumomab (blin" a toom' oh mab) is a mouse monoclonal IgG1 antibody that has bispecific reactivity to both the CD3 cell surface antigen that is found on normal T cells and the CD19 antigen that is overexpressed on B cell malignancies.
• The monoclonal antibody binds to T cells and brings them into contact with malignant B cells, allowing them to recognize and eliminate ALL blasts.
• Blinatumomab has been evaluated in children and adults with relapsed or refractory acute lymphoblastic leukemia (ALL) and shown to induce a high rate of clinical response and to prolong overall survival in comparison to conventional chemotherapy.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• known hypersensitivity to blinatumomab or to any component of the product formulation.

What drug interactions can this medicine cause?

• No formal drug interaction studies have been conducted with Blincyto.

Is this medicine FDA approved?

• This medicine is approved in the year 2014.

How should this medicine be used?

Recommended Dosage: For the 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).
• 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.

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).
• 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.

Administration

• Blincyto will be given to you by intravenous (IV) infusion into your vein by an infusion pump.
• Your healthcare provider will decide the number of treatment cycles of Blincyto.
• You will receive Blincyto by continuous IV infusion for 4 weeks (28 days), followed by a 2 week (14 days) break during which you will not receive Blincyto. This is 1 treatment cycle (42 days).

• Your healthcare provider may prescribe continued therapy.
• You will receive Blincyto by continuous IV infusion for 4 weeks (28 days), followed by an 8 week (56 days) break during which you will not receive Blincyto. This is 1 treatment cycle (84 days).

• Your healthcare provider may give you Blincyto in a hospital or clinic for the first 3 to 9 days of the first treatment cycle and for the first 2 days of the second cycle to check you for side effects. If you receive additional treatment cycles of Blincyto or if your treatment is stopped for a period of time and restarted, you may also be treated in a hospital or clinic.
• Your healthcare provider may change your dose of Blincyto, delay, or completely stop treatment with Blincyto if you have certain side effects.
• Your healthcare provider will do blood tests during treatment with Blincyto to check you for side effects.
• Before you receive Blincyto, you will be given a corticosteroid medicine to help reduce infusion reactions.
• It is very important to keep the area around the IV catheter clean to reduce the risk of getting an infection. Your healthcare provider will show you how to care for your catheter site.
• Do not change the settings on your infusion pump, even if there is a problem with your pump or your pump alarm sounds. Any changes to your infusion pump settings may cause a dose that is too high or too low to be given.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As injection: 35 mcg of lyophilized powder in a single-dose vial for reconstitution.

This medicine is available in fallowing brand namesː

• Blincyto

What side effects can this medication cause?

The most common side effects of this medicine include:

• infections
• low platelet count (thrombocytopenia)
• fever
• reactions related to infusion of the medicine such as face swelling, low blood pressure, and high blood pressure (infusion-related reactions)
• headache
• low red blood cell count (anemia)

Blincyto may cause serious side effects, including:

• Infections
• Low white blood cell counts (neutropenia)
• Abnormal liver blood tests
• Inflammation of the pancreas (pancreatitis)
• Cytokine Release Syndrome (CRS) and Infusion Reactions
• Neurologic problems

What special precautions should I follow?

• Do not drive, operate heavy machinery, or do other dangerous activities while you are receiving Blincyto because Blincyto can cause neurological symptoms, such as dizziness, seizures, and confusion.
• Infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections were observed in approximately 25% of patients, some of which were life-threatening or fatal. Monitor patients for signs or symptoms; treat appropriately.
• Fatal pancreatitis has been reported in patients receiving Blincyto in combination with dexamethasone. Evaluate patients who develop signs and symptoms of pancreatitis. Management of pancreatitis may require either temporary interruption or discontinuation of Blincyto.
• Strictly follow instructions for preparation (including admixing) and administration.
• Serious and fatal adverse reactions including "gasping syndrome" can occur in neonates and infants treated with benzyl alcohol-preserved drugs, including Blincyto (with preservative). Use Blincyto prepared with preservative-free saline for patients weighing less than 22 kg.
• Tumor lysis syndrome (TLS), which may be life-threatening or fatal, has been observed in patients receiving Blincyto. Monitor for signs or symptoms of TLS. Management of these events may require either temporary interruption or discontinuation of Blincyto
• Neutropenia and febrile neutropenia, including life-threatening cases, have been observed in patients receiving Blincyto. Monitor laboratory parameters (including, but not limited to, white blood cell count and absolute neutrophil count) during Blincyto infusion. Interrupt Blincyto if prolonged neutropenia occurs.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• cardiac failure event
• cytokine release syndrome (CRS)
• fever
• tremors
• headache

Management of overdosage:

• In the event of overdose, interrupt the infusion, monitor the patient for signs of adverse reactions, and provide supportive care.

Can this medicine be used in pregnancy?

• 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.

Can this medicine be used in children?

• The safety and efficacy of Blincyto have been established in pediatric patients with relapsed or refractory B-cell precursor ALL.

What are the active and inactive ingredients in this medicine?

• Active ingredient: blinatumomab
• Inactive ingredients: citric acid monohydrate, lysine hydrochloride, polysorbate 80, trehalose dihydrate, sodium hydroxide and preservative-free sterile water for injection.
• Inactive ingredients of IV Solution Stabilizer: citric acid monohydrate, lysine hydrochloride, polysorbate 80, sodium hydroxide and sterile water for injection.

Who manufactures and distributes this medicine?

Manufactured by: Amgen Inc., One Amgen Center Drive, Thousand Oaks

What should I know about storage and disposal of this medication?

• Intravenous (IV) bags containing Blincyto for infusion will arrive in a special package.
• Do not open the package.
• Do not freeze the package.
• The package containing Blincyto will be opened by your healthcare provider and stored in the refrigerator at 36°F to 46°F (2°C to 8°C) for up to 8 days.
• Do not throw away (dispose of) any Blincyto in your household trash. Talk with your healthcare provider about disposal of Blincyto and used supplies.
• Keep Blincyto and all medicines out of reach of children.

• Dailymed label info on Blinatumomab
• FDA Blinatumomab