Blincyto

• Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO and treat with corticosteroids as recommended

  [see

  2.4 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 4. Dosage Modifications for Adverse Reactions

  Adverse Reaction	GradeBased on the Common Terminology Criteria for Adverse Events (CTCAE). Grade 3 is severe, and Grade 4 is life-threatening.	Patients Weighing 45 kg or More	Patients Weighing Less Than 45 kg
  Cytokine Release Syndrome (CRS)	Grade 3	Interrupt BLINCYTO. Administer dexamethasone 8 mg every 8 hours intravenously or orally for up to 3 days and taper thereafter over 4 days. When CRS is resolved, restart BLINCYTO at 9 mcg/day, and escalate to 28 mcg/day after 7 days if the adverse reaction does not recur.	Interrupt BLINCYTO. Administer dexamethasone 5 mg/m2(maximum 8 mg) every 8 hours intravenously or orally for up to 3 days and taper thereafter over 4 days. When CRS is resolved, restart BLINCYTO 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 BLINCYTO permanently. Administer dexamethasone as instructed for Grade 3 CRS.
  Neurological Toxicity	Seizure	Discontinue BLINCYTO permanently if more than one seizure occurs.
  	Grade 2 ICANS	Interrupt BLINCYTO until ICANS resolves. Administer corticosteroids and manage according to current practice guidelines. When ICANS is resolved, restart BLINCYTO at 9 mcg/day. Escalate to 28 mcg/day after 7 days if the adverse reaction does not recur.	Interrupt BLINCYTO until ICANS resolves. Administer corticosteroids and manage according to current practice guidelines. When ICANS is resolved, restart BLINCYTO at 5 mcg/m2/day. Escalate to 15 mcg/m2/day after 7 days if the adverse reaction does not recur.
  	Grade 3 Neurologic Events including ICANS	Withhold BLINCYTO until no more than Grade 1 (mild) and for at least 3 days, then restart BLINCYTO at 9 mcg/day. Escalate to 28 mcg/day after 7 days if the adverse reaction does not recur. If the adverse reaction occurred at 9 mcg/day, or if the adverse reaction takes more than 7 days to resolve, discontinue BLINCYTO permanently.	Withhold BLINCYTO until no more than Grade 1 (mild) and for at least 3 days, then restart BLINCYTO at 5 mcg/m2/day. Escalate to 15 mcg/m2/day after 7 days if the adverse reaction does not recur. If the adverse reaction occurred at 5 mcg/m2/day, or if the adverse reaction takes more than 7 days to resolve, discontinue BLINCYTO permanently.
  		If ICANS, administer corticosteroids and manage according to current practice guidelines.
  	Grade 4	Discontinue BLINCYTO permanently.
  	Neurologic Events including ICANS	If ICANS, administer corticosteroids and manage according to current practice guidelines.
  Other Clinically Relevant Adverse Reactions	Grade 3	Withhold BLINCYTO until no more than Grade 1 (mild), then restart BLINCYTO at 9 mcg/day. Escalate to 28 mcg/day after 7 days if the adverse reaction does not recur. If the adverse reaction takes more than 14 days to resolve, discontinue BLINCYTO permanently.	Withhold BLINCYTO until no more than Grade 1 (mild), then restart BLINCYTO at 5 mcg/m2/day. Escalate to 15 mcg/m2/day after 7 days if the adverse reaction does not recur. If the adverse reaction takes more than 14 days to resolve, discontinue BLINCYTO permanently.
  	Grade 4	Consider discontinuing BLINCYTO permanently.

  ,

  5.1 Cytokine Release Syndrome

  Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. The median time to onset of CRS was 2 days after the start of infusion and the median time to resolution of CRS was 5 days among cases that resolved. Manifestations of CRS include fever, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin, and disseminated intravascular coagulation (DIC). The manifestations of CRS after treatment with BLINCYTO overlap with those of infusion reactions, capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS). Evaluation for HLH/MAS should be considered when CRS is atypical or prolonged, or when features of macrophage activation are present. Using all of these terms to define CRS in clinical trials of BLINCYTO, CRS was reported in 15% of patients with relapsed or refractory ALL, in 7% of patients with MRD-positive ALL, and in 16% of patients receiving BLINCYTO cycles in the consolidation phase of therapy

  [see Adverse Reactions (6.1)]

  .

  Monitor patients for signs or symptoms of these events. Advise outpatients on BLINCYTO to contact their healthcare professional for signs and symptoms associated with CRS. If severe CRS occurs, interrupt BLINCYTO until CRS resolves. Discontinue BLINCYTO permanently if life-threatening CRS occurs. Administer corticosteroids for severe or life-threatening CRS

  [see Dosage and Administration (2.4)]

  .

  ]

  .
• Neurological toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS) which may be severe, life-threatening, or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended

  [see

  2.4 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 4. Dosage Modifications for Adverse Reactions

  Adverse Reaction	GradeBased on the Common Terminology Criteria for Adverse Events (CTCAE). Grade 3 is severe, and Grade 4 is life-threatening.	Patients Weighing 45 kg or More	Patients Weighing Less Than 45 kg
  Cytokine Release Syndrome (CRS)	Grade 3	Interrupt BLINCYTO. Administer dexamethasone 8 mg every 8 hours intravenously or orally for up to 3 days and taper thereafter over 4 days. When CRS is resolved, restart BLINCYTO at 9 mcg/day, and escalate to 28 mcg/day after 7 days if the adverse reaction does not recur.	Interrupt BLINCYTO. Administer dexamethasone 5 mg/m2(maximum 8 mg) every 8 hours intravenously or orally for up to 3 days and taper thereafter over 4 days. When CRS is resolved, restart BLINCYTO 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 BLINCYTO permanently. Administer dexamethasone as instructed for Grade 3 CRS.
  Neurological Toxicity	Seizure	Discontinue BLINCYTO permanently if more than one seizure occurs.
  	Grade 2 ICANS	Interrupt BLINCYTO until ICANS resolves. Administer corticosteroids and manage according to current practice guidelines. When ICANS is resolved, restart BLINCYTO at 9 mcg/day. Escalate to 28 mcg/day after 7 days if the adverse reaction does not recur.	Interrupt BLINCYTO until ICANS resolves. Administer corticosteroids and manage according to current practice guidelines. When ICANS is resolved, restart BLINCYTO at 5 mcg/m2/day. Escalate to 15 mcg/m2/day after 7 days if the adverse reaction does not recur.
  	Grade 3 Neurologic Events including ICANS	Withhold BLINCYTO until no more than Grade 1 (mild) and for at least 3 days, then restart BLINCYTO at 9 mcg/day. Escalate to 28 mcg/day after 7 days if the adverse reaction does not recur. If the adverse reaction occurred at 9 mcg/day, or if the adverse reaction takes more than 7 days to resolve, discontinue BLINCYTO permanently.	Withhold BLINCYTO until no more than Grade 1 (mild) and for at least 3 days, then restart BLINCYTO at 5 mcg/m2/day. Escalate to 15 mcg/m2/day after 7 days if the adverse reaction does not recur. If the adverse reaction occurred at 5 mcg/m2/day, or if the adverse reaction takes more than 7 days to resolve, discontinue BLINCYTO permanently.
  		If ICANS, administer corticosteroids and manage according to current practice guidelines.
  	Grade 4	Discontinue BLINCYTO permanently.
  	Neurologic Events including ICANS	If ICANS, administer corticosteroids and manage according to current practice guidelines.
  Other Clinically Relevant Adverse Reactions	Grade 3	Withhold BLINCYTO until no more than Grade 1 (mild), then restart BLINCYTO at 9 mcg/day. Escalate to 28 mcg/day after 7 days if the adverse reaction does not recur. If the adverse reaction takes more than 14 days to resolve, discontinue BLINCYTO permanently.	Withhold BLINCYTO until no more than Grade 1 (mild), then restart BLINCYTO at 5 mcg/m2/day. Escalate to 15 mcg/m2/day after 7 days if the adverse reaction does not recur. If the adverse reaction takes more than 14 days to resolve, discontinue BLINCYTO permanently.
  	Grade 4	Consider discontinuing BLINCYTO permanently.

  ,

  5.2 Neurological Toxicities, including Immune Effector Cell-Associated Neurotoxicity Syndrome

  BLINCYTO can cause serious or life-threatening neurologic toxicity, including ICANS

  [see Adverse Reactions 6.1]

  .

  The incidence of neurologic toxicities in clinical trials was approximately 65%

  [see Adverse Reactions (6.1)]

  . Among patients that experienced a neurologic toxicity, the median time to the first event was within the first 2 weeks of BLINCYTO treatment. The most common (≥ 10%) manifestations of neurological toxicity were headache, and tremor; the neurological toxicity profile varied by age group

  [see Use in Specific Populations (8.4, 8.5)]

  . Grade 3 or higher neurological toxicities following initiation of BLINCYTO administration occurred in approximately 13% of patients and included encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. The majority of neurologic toxicities resolved following interruption of BLINCYTO, but some resulted in treatment discontinuation.

  The incidence of signs and symptoms consistent with ICANS in clinical trials was 7.5%. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.

  There is limited experience with BLINCYTO in patients with active ALL in the central nervous system (CNS) or a history of neurologic events. Patients with a history or presence of clinically relevant CNS pathology were excluded from clinical studies. Patients with Down Syndrome may have a higher risk of seizures with BLINCYTO therapy; consider seizure prophylaxis prior to initiation of BLINCYTO for these patients.

  Monitor patients receiving BLINCYTO for signs and symptoms of neurological toxicities, including ICANS. Advise outpatients on BLINCYTO to contact their healthcare professional if they develop signs or symptoms of neurological toxicities. Management of neurologic toxicity may require interruption or discontinuation of BLINCYTO as recommended and/or treatment with corticosteroids

  [see Dosage and Administration (2.4)]

  .

  ]

  .

BLINCYTO is a bispecific CD19-directed CD3 T-cell engager indicated for the treatment of adult and pediatric patients one month and older with:

• CD19-positive 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%. (
  1.1 MRD-positive B-cell Precursor ALL

  BLINCYTO is indicated for the treatment of CD19-positive 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 adult and pediatric patients one month and older.
  )
• Relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL). (
  1.2 Relapsed or Refractory B-cell Precursor ALL

  BLINCYTO is indicated for the treatment of relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients one month and older.
  )
• CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (ALL) in the consolidation phase of multiphase chemotherapy. (
  1.3 B-cell Precursor ALL in the Consolidation Phase

  BLINCYTO is indicated for the treatment of CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (ALL) in the consolidation phase of multiphase chemotherapy in adult and pediatric patients one month and older.
  )

• For the treatment of MRD-positive B-cell Precursor ALL
  • -See Full Prescribing Information for recommended dose by patient weight and schedule. (
    2.1 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 1for 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

    Cycle	Patients Weighing 45 kg or More (Fixed-dose)	Patients Weighing Less Than 45 kg (BSA-based dose)
    Induction Cycle 1
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval
    Consolidation Cycles 2-4
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval

    • 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.
    • Intrathecal chemotherapy prophylaxis is recommended before and during BLINCYTO therapy to prevent central nervous system ALL relapse.
    • 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/m²of dexamethasone intravenously or orally, 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 Instructions for Use for infusion over 24 hours or 48 hours.
      • See Instructions for Use for infusion over 72 hours, 96 hours, or 7 days using Bacteriostatic 0.9% Sodium Chloride Injection (containing 0.9% benzyl alcohol). The administration of BLINCYTO as a 72-hour, 96-hour, and 7-day infusion is not recommended for patients weighing less than 5.4 kg.
    )
  • -Hospitalization is recommended for the first 3 days of the first cycle and the first 2 days of the second cycle. (
    2.1 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 1for 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

    Cycle	Patients Weighing 45 kg or More (Fixed-dose)	Patients Weighing Less Than 45 kg (BSA-based dose)
    Induction Cycle 1
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval
    Consolidation Cycles 2-4
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval

    • 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.
    • Intrathecal chemotherapy prophylaxis is recommended before and during BLINCYTO therapy to prevent central nervous system ALL relapse.
    • 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/m²of dexamethasone intravenously or orally, 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 Instructions for Use for infusion over 24 hours or 48 hours.
      • See Instructions for Use for infusion over 72 hours, 96 hours, or 7 days using Bacteriostatic 0.9% Sodium Chloride Injection (containing 0.9% benzyl alcohol). The administration of BLINCYTO as a 72-hour, 96-hour, and 7-day infusion is not recommended for patients weighing less than 5.4 kg.
    )
  • -Premedicate with prednisone or equivalent dexamethasone. (
    2.1 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 1for 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

    Cycle	Patients Weighing 45 kg or More (Fixed-dose)	Patients Weighing Less Than 45 kg (BSA-based dose)
    Induction Cycle 1
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval
    Consolidation Cycles 2-4
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval

    • 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.
    • Intrathecal chemotherapy prophylaxis is recommended before and during BLINCYTO therapy to prevent central nervous system ALL relapse.
    • 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/m²of dexamethasone intravenously or orally, 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 Instructions for Use for infusion over 24 hours or 48 hours.
      • See Instructions for Use for infusion over 72 hours, 96 hours, or 7 days using Bacteriostatic 0.9% Sodium Chloride Injection (containing 0.9% benzyl alcohol). The administration of BLINCYTO as a 72-hour, 96-hour, and 7-day infusion is not recommended for patients weighing less than 5.4 kg.
    )
• For the treatment of Relapsed or Refractory B-cell Precursor ALL
  • -See Full Prescribing Information for recommended dose by patient weight and schedule. (
    2.2 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 2for 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

    Cycle	Patients Weighing 45 kg or More (Fixed-dose)	Patients Weighing Less Than 45 kg (BSA-based dose)
    	Induction Cycle 1
    Days 1-7	9 mcg/day	5 mcg/m2/day (not to exceed 9 mcg/day)
    Days 8-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval
    Induction Cycle 2
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval
    Consolidation Cycles 3-5
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval
    Continued Therapy Cycles 6-9
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-84	56-day treatment-free interval	56-day treatment-free interval

    • 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-initiations (e.g., if treatment is interrupted for 4 or more hours), supervision by a healthcare professional or hospitalization is recommended.
    • Intrathecal chemotherapy prophylaxis is recommended before and during BLINCYTO therapy to prevent central nervous system ALL relapse.
    • Premedicate with dexamethasone:
      • For adult patients, premedicate with 20 mg of dexamethasone intravenously or orally 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/m²of dexamethasone intravenously or orally, 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 Instructions for Use for infusion over 24 hours or 48 hours.
      • See Instructions for Use for infusion over 72 hours, 96 hours, or 7 days using Bacteriostatic 0.9% Sodium Chloride Injection (containing 0.9% benzyl alcohol). The administration of BLINCYTO as a 72-hour, 96-hour, and 7-day infusion is not recommended for patients weighing less than 5.4 kg.
    )
  • -Hospitalization is recommended for the first 9 days of the first cycle and the first 2 days of the second cycle. (
    2.2 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 2for 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

    Cycle	Patients Weighing 45 kg or More (Fixed-dose)	Patients Weighing Less Than 45 kg (BSA-based dose)
    	Induction Cycle 1
    Days 1-7	9 mcg/day	5 mcg/m2/day (not to exceed 9 mcg/day)
    Days 8-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval
    Induction Cycle 2
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval
    Consolidation Cycles 3-5
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval
    Continued Therapy Cycles 6-9
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-84	56-day treatment-free interval	56-day treatment-free interval

    • 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-initiations (e.g., if treatment is interrupted for 4 or more hours), supervision by a healthcare professional or hospitalization is recommended.
    • Intrathecal chemotherapy prophylaxis is recommended before and during BLINCYTO therapy to prevent central nervous system ALL relapse.
    • Premedicate with dexamethasone:
      • For adult patients, premedicate with 20 mg of dexamethasone intravenously or orally 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/m²of dexamethasone intravenously or orally, 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 Instructions for Use for infusion over 24 hours or 48 hours.
      • See Instructions for Use for infusion over 72 hours, 96 hours, or 7 days using Bacteriostatic 0.9% Sodium Chloride Injection (containing 0.9% benzyl alcohol). The administration of BLINCYTO as a 72-hour, 96-hour, and 7-day infusion is not recommended for patients weighing less than 5.4 kg.
    )
  • -Premedicate with dexamethasone. (
    2.2 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 2for 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

    Cycle	Patients Weighing 45 kg or More (Fixed-dose)	Patients Weighing Less Than 45 kg (BSA-based dose)
    	Induction Cycle 1
    Days 1-7	9 mcg/day	5 mcg/m2/day (not to exceed 9 mcg/day)
    Days 8-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval
    Induction Cycle 2
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval
    Consolidation Cycles 3-5
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval
    Continued Therapy Cycles 6-9
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-84	56-day treatment-free interval	56-day treatment-free interval

    • 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-initiations (e.g., if treatment is interrupted for 4 or more hours), supervision by a healthcare professional or hospitalization is recommended.
    • Intrathecal chemotherapy prophylaxis is recommended before and during BLINCYTO therapy to prevent central nervous system ALL relapse.
    • Premedicate with dexamethasone:
      • For adult patients, premedicate with 20 mg of dexamethasone intravenously or orally 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/m²of dexamethasone intravenously or orally, 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 Instructions for Use for infusion over 24 hours or 48 hours.
      • See Instructions for Use for infusion over 72 hours, 96 hours, or 7 days using Bacteriostatic 0.9% Sodium Chloride Injection (containing 0.9% benzyl alcohol). The administration of BLINCYTO as a 72-hour, 96-hour, and 7-day infusion is not recommended for patients weighing less than 5.4 kg.
    )
• For the treatment of B-cell Precursor ALL in the Consolidation Phase
  • -See Full Prescribing Information for recommended dose by patient weight and schedule. (
    2.3 Treatment of B-cell Precursor ALL in the Consolidation Phase

    • A single cycle of BLINCYTO monotherapy in consolidation is 28 days of continuous infusion followed by a 14-day treatment-free interval (total 42 days)

      [see Table 3and Clinical Studies (14.3)]

      .
    • 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 (see Table 3).

    Table 3. Recommended BLINCYTO Dose and Schedule in the Consolidation Phase of Treatment of B-cell Precursor ALL

    BLINCYTO Consolidation Cycle	Patients Weighing 45 kg or More (Fixed-dose)	Patients Weighing Less Than 45 kg (BSA-based dose)
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval

    • 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.
    • Intrathecal chemotherapy prophylaxis is recommended before and during BLINCYTO therapy to prevent central nervous system ALL relapse.
    • Premedicate with dexamethasone:
      • For adult patients, premedicate with dexamethasone 20 mg intravenously within 1 hour prior to the first dose of BLINCYTO of each cycle.
      • For pediatric patients, premedicate with 5 mg/m²of dexamethasone intravenously or orally, 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 Instructions for Use for infusion over 24 hours or 48 hours.
      • See Instructions for Use for infusion over 72 hours, 96 hours, or 7 days using Bacteriostatic 0.9% Sodium Chloride Injection (containing 0.9% benzyl alcohol). The administration of BLINCYTO as a 72-hour, 96-hour, and 7-day infusion is not recommended for patients weighing less than 5.4 kg.
    )
  • -Hospitalization is recommended for the first 3 days of the first cycle and the first 2 days of the second cycle. (
    2.3 Treatment of B-cell Precursor ALL in the Consolidation Phase

    • A single cycle of BLINCYTO monotherapy in consolidation is 28 days of continuous infusion followed by a 14-day treatment-free interval (total 42 days)

      [see Table 3and Clinical Studies (14.3)]

      .
    • 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 (see Table 3).

    Table 3. Recommended BLINCYTO Dose and Schedule in the Consolidation Phase of Treatment of B-cell Precursor ALL

    BLINCYTO Consolidation Cycle	Patients Weighing 45 kg or More (Fixed-dose)	Patients Weighing Less Than 45 kg (BSA-based dose)
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval

    • 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.
    • Intrathecal chemotherapy prophylaxis is recommended before and during BLINCYTO therapy to prevent central nervous system ALL relapse.
    • Premedicate with dexamethasone:
      • For adult patients, premedicate with dexamethasone 20 mg intravenously within 1 hour prior to the first dose of BLINCYTO of each cycle.
      • For pediatric patients, premedicate with 5 mg/m²of dexamethasone intravenously or orally, 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 Instructions for Use for infusion over 24 hours or 48 hours.
      • See Instructions for Use for infusion over 72 hours, 96 hours, or 7 days using Bacteriostatic 0.9% Sodium Chloride Injection (containing 0.9% benzyl alcohol). The administration of BLINCYTO as a 72-hour, 96-hour, and 7-day infusion is not recommended for patients weighing less than 5.4 kg.
    )
  • -Premedicate with dexamethasone. (
    2.3 Treatment of B-cell Precursor ALL in the Consolidation Phase

    • A single cycle of BLINCYTO monotherapy in consolidation is 28 days of continuous infusion followed by a 14-day treatment-free interval (total 42 days)

      [see Table 3and Clinical Studies (14.3)]

      .
    • 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 (see Table 3).

    Table 3. Recommended BLINCYTO Dose and Schedule in the Consolidation Phase of Treatment of B-cell Precursor ALL

    BLINCYTO Consolidation Cycle	Patients Weighing 45 kg or More (Fixed-dose)	Patients Weighing Less Than 45 kg (BSA-based dose)
    Days 1-28	28 mcg/day	15 mcg/m2/day (not to exceed 28 mcg/day)
    Days 29-42	14-day treatment-free interval	14-day treatment-free interval

    • 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.
    • Intrathecal chemotherapy prophylaxis is recommended before and during BLINCYTO therapy to prevent central nervous system ALL relapse.
    • Premedicate with dexamethasone:
      • For adult patients, premedicate with dexamethasone 20 mg intravenously within 1 hour prior to the first dose of BLINCYTO of each cycle.
      • For pediatric patients, premedicate with 5 mg/m²of dexamethasone intravenously or orally, 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 Instructions for Use for infusion over 24 hours or 48 hours.
      • See Instructions for Use for infusion over 72 hours, 96 hours, or 7 days using Bacteriostatic 0.9% Sodium Chloride Injection (containing 0.9% benzyl alcohol). The administration of BLINCYTO as a 72-hour, 96-hour, and 7-day infusion is not recommended for patients weighing less than 5.4 kg.
    )
• Refer to Full Prescribing Information for important preparation and administration information. (
  2.5 Preparation and Administration of BLINCYTO

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

  [see Warnings and Precautions (5.10)]

  .

  BLINCYTO can be infused over 24 hours (preservative-free), 48 hours (preservative-free), 72 hours (with preservative), 96 hours (with preservative), or 7 days (with preservative). The choice between these options for the infusion duration should be made by the treating healthcare provider considering the frequency of the infusion bag changes and the weight of the patient. The administration of BLINCYTO as a 72-hour, 96-hour, and 7-day infusion is not recommended for patients weighing less than 5.4 kg.

  For preparation, reconstitution, and administration of BLINCYTO:

  The BLINCYTO Instructions for Use contains more detailed instructions on the preparation of infusion

  [see Instructions for Use]

  .

  The preparation steps differ based on the infusion duration. Follow the steps specific to the infusion duration you are preparing.

  Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

  Call 1-800-77-AMGEN (1-800-772-6436) if you have questions about the reconstitution and preparation of BLINCYTO.
  )
• Administer as a continuous intravenous infusion at a constant flow rate using an infusion pump.
  • -See Instructions for Use for infusion over 24 hours or 48 hours.
  • -See Instructions for Use for infusion over 72 hours, 96 hours, or 7 days using Bacteriostatic 0.9% Sodium Chloride Injection (containing 0.9% benzyl alcohol). This option is not recommended for patients weighing less than 5.4 kg.

For injection: 35 mcg of white to off-white lyophilized powder in a single-dose vial for reconstitution.

Based on its mechanism of action, BLINCYTO may cause fetal harm when administered to a pregnant woman

Blinatumomab causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. In addition, based on expression of CD19 on B-cells and the finding of B-cell depletion in non-pregnant animals, blinatumomab can cause B-cell lymphocytopenia in infants exposed to blinatumomab in-utero. Advise pregnant women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.