Indication

BLINCYTO® is indicated for the treatment of B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adults and children.

This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

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Preparing BLINCYTO®

Package contents and storage

BLINCYTO® package contents and vials

Each BLINCYTO® package contains:1

  • One BLINCYTO® vial supplied in a single-dose vial as a sterile, preservative-free, white to off-white lyophilized powder (35 mcg of BLINCYTO®/vial)
  • One Intravenous Solution Stabilizer (IVSS) vial supplied in a 10 mL single-dose glass vial as a sterile, preservative-free, colorless to slightly yellow, clear solution
    • The IVSS is injected into the IV bag prior to the addition of reconstituted BLINCYTO® to prevent adhesion of BLINCYTO® to the IV bags and IV tubing
    • Do not use the IVSS to reconstitute BLINCYTO®

NOTE: The package does not include preservative-free Sterile Water for Injection, USP, which should be used to reconstitute the lyophilized BLINCYTO® powder.

Please see full Prescribing Information for complete reconstitution and preparation instructions.

Storage and handling of BLINCYTO® and IVSS vials1

Refrigerate vials of BLINCYTO® and IVSS at 2°C to 8°C (36°F to 46°F) in the original packaging.

Do not freeze.

Protect the vials of BLINCYTO® and IVSS from light until time of use.

What you need to know to prepare BLINCYTO®

The information provided here is an abbreviated summary and does not replace the Prescribing Information. Please consult the Prescribing Information when preparing BLINCYTO®. 

Aseptic preparation and admixing area checklist1

Strictly observe aseptic technique when preparing the solution for infusion since BLINCYTO® vials do not contain antimicrobial preservatives. To prevent accidental contamination, prepare BLINCYTO® according to aseptic standards, including but not limited to:

  • Prepare BLINCYTO® in a USP <797> compliant facility
  • Prepare BLINCYTO® in an ISO Class 5 laminar flow hood or better
  • Ensure that the admixing area has appropriate environmental specifications, confirmed by periodic monitoring
  • Ensure that personnel are appropriately trained in aseptic manipulations and admixing of oncology drugs
  • Ensure that personnel wear appropriate protective clothing and gloves
  • Ensure that gloves and surfaces are disinfected

Preparation of BLINCYTO® solution for 24- or 48-hour infusion

In order to prepare BLINCYTO® solution for a 24- or 48-hour infusion, you will need to know:1

  • The prescribed dose
  • The infusion duration
  • BSA for patients weighing less than 45 kg

It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).

Before preparation, ensure that you have the following supplies ready:1

  • Patients weighing greater than or equal to 45 kg:
    • 1 package of BLINCYTO® is needed for preparation of 28 mcg/day dose infused over 24 hours at a rate of 10 mL/hour
    • 2 packages of BLINCYTO® are needed for preparation of 28 mcg/day dose infused over 48 hours at a rate of 5 mL/hour
  • Patients weighing less than 45 kg:
    • 1 package of BLINCYTO® is needed for preparation of 15 mcg/m2/day dose infused over 24 hours at a rate of 10 mL/hour
    • 2 packages of BLINCYTO® are needed for preparation of 15 mcg/m2/day dose infused over 48 hours at a rate of 5 mL/hour for patients with a BSA greater than 1.09 m2

The following supplies are also required, but not included in the package:1

  • Supplies to make a 270 mL 0.9% Sodium Chloride IV bag
    • An empty IV bag (use only polyvinyl chloride [PVC] di-ethylhexylphthalate-free [DEHP-free], polyolefin, or ethyl vinyl acetate [EVA] infusion bags/pump cassettes)
    • 0.9% Sodium Chloride Injection, USP (eg, 1000 mL)
  • Preservative-free Sterile Water for Injection, USP
  • PVC DEHP-free, polyolefin, or EVA IV tubing with a sterile, nonpyrogenic, low protein-binding 0.2-micron in-line filter
    • Ensure that the IV tubing is compatible with the infusion pump

Special considerations for 24- or 48-hour BLINCYTO® infusion bags1

  • IVSS is provided with the BLINCYTO® package and is used to coat the IV bag prior to addition of reconstituted BLINCYTO® to prevent adhesion of BLINCYTO® to IV bags and IV tubing. Therefore, add IVSS to the IV bag containing 0.9% Sodium Chloride Injection, USP. Do not use IVSS for reconstitution of BLINCYTO®
  • The entire volume of the admixed BLINCYTO® will be more than the volume administered to the patient (240 mL) to account for the priming of the IV tubing and to ensure that the patient will receive the full dose of BLINCYTO®
  • When preparing an IV bag, remove air from IV bag. This is particularly important for use with an ambulatory infusion pump
  • Use the specific volumes described in the admixing instructions in the full Prescribing Information to minimize errors

Preparation of the BLINCYTO® infusion bag1

Verify the prescribed dose and infusion duration for each BLINCYTO® infusion bag. To minimize errors, use the specific volumes described in the table below to prepare the BLINCYTO® infusion bag.

1.

Aseptically add 270 mL of 0.9% Sodium Chloride Injection, USP to the IV bag.

2.

Aseptically transfer 5.5 mL of IVSS to the IV bag containing 0.9% Sodium Chloride Injection, USP.

  • Gently mix the contents of the bag to avoid foaming. Discard the vial containing the unused IVSS
3.

Aseptically transfer the pre-calculated volume of reconstituted BLINCYTO® into the IV bag containing 0.9% Sodium Chloride Injection, USP and IVSS.

  • Use the table below to determine the specific volume of reconstituted BLINCYTO® required for the prescribed dose and duration*
  • Gently mix the contents of the bag to avoid foaming

For patients receiving a 24- or 48-hour infusion: Volume to add to IV bag1

0.9% Sodium Chloride injection, USP (starting volume)270 mL
IVSS5.5 mL
For patients weighing ≥ 45 kg (fixed dose)*
DoseNumber of BLINCYTO® packagesReconstituted BLINCYTO®

28 mcg/day

Infused over 24 hours at a rate of 10 mL/hour

12.6 mL

28 mcg/day

Infused over 48 hours at a rate of 5 mL/hour

25.2 mL
For patients weighing < 45 kg (BSA‐based dose)*
Infusion duration and rateBSA (m2­)Number of BLINCYTO® packagesReconstituted BLINCYTO®

15 mcg/m2/day

Infused over 24 hours at a rate of 10 mL/hour

1.5–1.5912.1 mL
1.4–1.491 2 mL
1.3–1.391 1.8 mL
1.2–1.291 1.7 mL
1.1–1.191 1.6 mL
1–1.091 1.4 mL
0.9–0.991 1.3 mL
0.8–0.891 1.1 mL
0.7–0.791 1 mL
0.6–0.691 0.86 mL
0.5–0.591 0.72 mL
0.4–0.491 0.59 mL
Infusion duration and rateBSA (m)Number of BLINCYTO® packagesReconstituted BLINCYTO®

15 mcg/m2/day

Infused over 48 hours at a rate of 5 mL/hour

1.5–1.5924.2 mL
1.4–1.4923.9 mL
1.3–1.3923.7 mL
1.2–1.2923.4 mL
1.1–1.1923.1 mL
1–1.0912.8 mL
0.9–0.9912.6 mL
0.8–0.8912.3 mL
0.7–0.7912 mL
0.6–0.6911.7 mL
0.5–0.5911.4 mL
0.4–0.4911.2 mL
4.

Under aseptic conditions, attach the IV tubing to the IV bag with the sterile 0.2-micron in-line filter.

  • Use only PVC DEHP-free, polyolefin or EVA IV tubing with a sterile, nonpyrogenic, low protein-binding 0.2-micron in-line filter
  • Ensure that the IV tubing is compatible with the infusion pump
5.

Remove air from the IV bag. This is particularly important for use with an ambulatory infusion pump.

  • Prime the IV tubing only with the prepared solution for infusion
  • Do not prime with 0.9% Sodium Chloride Injection, USP
6.

Store at 2°C to 8°C (36°F to 46°F) if not used immediately.

Additional storage directions and maximum storage times are listed in the BLINCYTO® Prescribing Information.

IMPORTANT NOTE: Do not flush the BLINCYTO® infusion line or IV catheter, especially when changing infusion bags. Flushing when changing bags or at completion of infusion can result in excess dosage and complications thereof. When administering via a multilumen venous catheter, BLINCYTO® should be infused through a dedicated lumen.

Preparation of BLINCYTO® solution for 7-day infusion

In order to prepare BLINCYTO® solution for a 7-day infusion, you will need to know:1

  • The prescribed dose
  • The infusion duration
  • BSA for patients weighing greater than or equal to 22 kg and less than 45 kg

It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).

Before preparation, ensure that you have the following supplies ready:1

  • Patients weighing greater than or equal to 45 kg:
    • 6 packages of BLINCYTO® are needed for preparation of 28 mcg/day dose infused over 7 days at a rate of 0.6 mL/hour
  • Patients weighing greater than or equal to 22 kg and less than 45 kg:
    • 4 or 5 packages of BLINCYTO® are needed for preparation of 15 mcg/m2/day dose infused over 7 days at a rate of 0.6 mL/hour
    • IMPORTANT NOTE: This option is not recommended for use in patients weighing less than 22 kg

The following supplies are also required, but not included in the package:1

  • Supplies to make a 110 mL 0.9% Sodium Chloride IV bag
    • An empty IV bag (use only PVC DEHP-free, polyolefin, or EVA infusion bags/pump cassettes)
    • Bacteriostatic 0.9% Sodium Chloride, USP
    • 0.9% Sodium Chloride Injection, USP (eg, 1000 mL)
  • Preservative-free Sterile Water for Injection, USP
  • PVC DEHP-free, polyolefin, or EVA IV tubing
    • Ensure that the IV tubing is compatible with the infusion pump

Special considerations for a 7-day BLINCYTO® infusion bag1

  • IVSS is provided with the BLINCYTO® package and is used to coat the IV bag prior to addition of reconstituted BLINCYTO® to prevent adhesion of BLINCYTO® to IV bags and IV tubing. Therefore, add IVSS to the IV bag containing bacteriostatic saline. Do not use IVSS for reconstitution of BLINCYTO®
  • The entire volume of the admixed BLINCYTO® will be more than the volume administered to the patient (100 mL) to account for the priming of the IV tubing and to ensure that the patient will receive the full dose of BLINCYTO®
  • When preparing an IV bag, remove air from IV bag. This is particularly important for use with an ambulatory infusion pump
  • Use the specific volumes described in the admixing instructions in the full Prescribing Information to minimize errors

Preparation of the BLINCYTO® infusion bag1

When preparing BLINCYTO® solution for infusion, it is important to remember the volume of reconstituted BLINCYTO® used differs depending on the dose, infusion duration, and patient's weight/BSA.

Verify the prescribed dose and infusion duration for each BLINCYTO® infusion bag. To minimize errors, use the specific volumes described in the table below to prepare the BLINCYTO® infusion bag.

1.

Aseptically add 90 mL Bacteriostatic 0.9% Sodium Chloride, USP to the IV bag.

2.

Aseptically transfer 2.2 mL of IVSS to the IV bag containing the saline solution.

  • Gently mix the contents of the bag to avoid foaming. Discard the vial containing the unused IVSS
3.

Aseptically transfer the pre-calculated volume of reconstituted BLINCYTO® into the IV bag containing the saline solution and IVSS.

  • Use the table below to determine the specific volume of reconstituted BLINCYTO® required for the prescribed dose
  • Gently mix the contents of the bag to avoid foaming

For patients receiving a 7-day infusion: Volume to add to IV bag1

Bacteriostatic 0.9% Sodium Chloride (starting volume)90 mL
IVSS2.2 mL
For patients weighing greater than or equal to 45 kg (fixed dose)
DoseNumber of BLINCYTO® packagesReconstituted BLINCYTO®0.9% Sodium Chloride, USP to qs to a final volume of 110 mL§

28 mcg/day

Infused over 7 days
at a rate of 0.6 mL/hour

616.8 mL1 mL
For patients weighing 22–45 kg (BSA-based dose)
DoseBSA (m2)Number of BLINCYTO® packagesReconstituted BLINCYTO®0.9% Sodium Chloride, USP to qs to a final volume of 110 mL§

15 mcg/m2/day

Infused over 7 days
at a rate of 0.6 mL/hour

1.5–1.59514 mL3.8 mL
1.4–1.49513.1 mL4.7 mL
1.3–1.39512.2 mL5.6 mL
1.2–1.29511.3 mL6.5 mL
1.1–1.19410.4 mL7.4 mL
1–1.0949.5 mL8.3 mL
0.9–0.9948.6 mL9.2 mL
4.

Aseptically transfer the pre-calculated volume of 0.9% Sodium Chloride, USP to the IV bag to a final volume of 110 mL resulting in 0.74% benzyl alcohol.

  • Use the table above to determine the specific volume of 0.9% Sodium Chloride Injection, USP
  • Gently mix the contents of the bag to avoid foaming
5.

Under aseptic conditions, attach the IV tubing to the IV bag. An in-line filter is not required for a 7-day bag.

  • Ensure that the IV tubing is compatible with the infusion pump
6.

Remove air from the IV bag. This is particularly important for use with an ambulatory infusion pump.

  • Prime the IV tubing only with the prepared solution for infusion
  • Do not prime with 0.9% Sodium Chloride Injection, USP
7.

Store at 2°C to 8°C (36°F to 46°F) if not used immediately.

Additional storage directions and maximum storage times are listed in the BLINCYTO® Prescribing Information.

IMPORTANT NOTE: Do not flush the BLINCYTO® infusion line or IV catheter, especially when changing infusion bags. Flushing when changing bags or at completion of infusion can result in excess dosage and complications thereof. When administering via a multilumen venous catheter, BLINCYTO® should be infused through a dedicated lumen.

Reconstitution of BLINCYTO®1

1.

Add 3 mL of preservative-free Sterile Water for Injection, USP by directing the water along the walls of the BLINCYTO® vial and not directly on the lyophilized powder (resulting in a final BLINCYTO® concentration of 12.5 mcg/mL).

  • Do not reconstitute BLINCYTO® with IVSS
2.

Gently swirl the contents to avoid excess foaming. Do not shake.

3.

Visually inspect the reconstituted solution for particulate matter and discoloration during reconstitution and prior to infusion. The resulting solution should be clear to slightly opalescent, colorless to slightly yellow. Do not use if solution is cloudy or has precipitated.

The information provided here is an abbreviated summary and does not replace the Prescribing Information. Please consult the Prescribing Information when preparing BLINCYTO®. 

Reference: 1. BLINCYTO® (blinatumomab) prescribing information, Amgen.

IMPORTANT SAFETY INFORMATION

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.
Contraindications

BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions
  • Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in 15% of patients with R/R ALL and in 7% of patients with MRD-positive ALL. The median time to onset of CRS is 2 days after the start of infusion. Closely monitor and advise patients to contact their healthcare professional for signs and symptoms of serious adverse events such as fever, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), and disseminated intravascular coagulation (DIC). The manifestations of CRS after treatment with BLINCYTO® overlap with those of infusion reactions, capillary leak syndrome, and hemophagocytic histiocytosis/macrophage activation syndrome. If severe CRS occurs, interrupt BLINCYTO® until CRS resolves. Discontinue BLINCYTO® permanently if life-threatening CRS occurs.
  • Neurological Toxicities: Approximately 65% of patients receiving BLINCYTO® in clinical trials experienced neurological toxicities. The median time to the first event was within the first 2 weeks of BLINCYTO® treatment and the majority of events resolved. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO® as outlined in the PI.
  • Infections: Approximately 25% of patients receiving BLINCYTO® in clinical trials experienced serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO® as needed.
  • Tumor Lysis Syndrome (TLS), which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO® treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO® as needed to manage these events.
  • Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters (including, but not limited to, white blood cell count and absolute neutrophil count) during BLINCYTO® infusion and interrupt BLINCYTO® if prolonged neutropenia occurs.
  • Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO® are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO® is being administered.
  • Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO® treatment with a median time to onset of 3 days. In patients receiving BLINCYTO®, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 19 days. Grade 3 or greater elevations in liver enzymes occurred in approximately 7% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase, and TBILI prior to the start of and during BLINCYTO® treatment. BLINCYTO® treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
  • Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO® in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO® and dexamethasone as needed.
  • Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO®, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.
  • Preparation and administration errors have occurred with BLINCYTO® treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
  • Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO® treatment, during treatment, and until immune recovery following last cycle of BLINCYTO®.
  • Risk of Serious Adverse Reactions in Pediatric Patients due to Benzyl Alcohol Preservative: Serious and fatal adverse reactions including “gasping syndrome,” which is characterized by central nervous system depression, metabolic acidosis, and gasping respirations, can occur in neonates and infants treated with benzyl alcohol-preserved drugs including BLINCYTO® (with preservative). When prescribing BLINCYTO® (with preservative) for pediatric patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO® (with preservative) and other drugs containing benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known. Due to the addition of bacteriostatic saline, 7-day bags of BLINCYTO® solution for infusion with preservative contain benzyl alcohol and are not recommended for use in any patients weighing < 22 kg.
Adverse Reactions
  • The most common adverse reactions (≥ 20%) in clinical trial experience of patients with MRD-positive B-cell precursor ALL (BLAST Study) treated with BLINCYTO® were pyrexia (91%), infusion-related reactions (77%), headache (39%), infections (pathogen unspecified [39%]), tremor (31%), and chills (28%). Serious adverse reactions were reported in 61% of patients. The most common serious adverse reactions (≥ 2%) included pyrexia, tremor, encephalopathy, aphasia, lymphopenia, neutropenia, overdose, device related infection, seizure, and staphylococcal infection.
  • Adverse reactions that were observed more frequently (≥ 10%) in the pediatric population compared to the adults with relapsed or refractory B-cell precursor ALL were pyrexia (80% vs. 61%), hypertension (26% vs. 8%), anemia (41% vs. 24%), infusion-related reaction (49% vs. 34%), thrombocytopenia (34% vs. 21%), leukopenia (24% vs. 11%), and weight increased (17% vs. 6%).
  • In pediatric patients less than 2 years old (infants), the incidence of neurologic toxicities was not significantly different than for the other age groups, but its manifestations were different; the only event terms reported were agitation, headache, insomnia, somnolence, and irritability. Infants also had an increased incidence of hypokalemia (50%) compared to other pediatric age cohorts (15-20%) or adults (17%).
Dosage and Administration Guidelines
  • BLINCYTO® is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
  • It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
INDICATION

BLINCYTO® is indicated for the treatment of B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adults and children.

This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide, for BLINCYTO®.

BLINCYTO® is a registered trademark of Amgen Inc.