tagraxofusp (Rx)

Blastic Plasmacytoid Dendritic Cell Neoplasm

CD123-directed cytotoxin for treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN)

Each cycle is 21 days

Premedicate with H1-histamine antagonist, H2- histamine antagonist, corticosteroid, and acetaminophen 60 minutes before each dose

Days 1-5: 12 mcg/kg IV qDay

Continue treatment until disease progression or unacceptable toxicity

Dosing period may be extended for dose delays up to Day 10 of the cycle

Dosage Modifications

Dosage modifications based on parameter and severity criteria

• ALT or AST increase >5x ULN: Withhold until AST/ALT ≤2.5x ULN
• Serum creatinine >1.8 mg/dL or CrCl ≤60 mL/min: Withhold until serum creatinine ≤1.8 mg/dL or CrCl ≥60 mL/min
• Systolic blood pressure (SBP) ≥160 mm Hg or ≤80 mm Hg: Withhold until SBP <160 mm Hg or >80 mm Hg
• Heart rate (HR) ≥130 bpm or ≤40 bpm: Withhold until HR is <130 bpm or >40 bpm
• Body temperature ≥38°C: Withhold until body temperature <38°C

• Hypersensitivity reactions

  • Mild or moderate: Withhold until any mild or moderate hypersensitivity reaction resolves; resume at the same infusion rate
  • Severe or life-threatening: Discontinue permanently

Capillary leak syndrome (CLS) guidelines

• Before first dose in Cycle 1

  • Serum albumin <3.2 g/dL: Administer when serum albumin ≥3.2 g/dL

• During treatment

  • Interrupt dosing until relevant CLS sign/symptom resolves while implementing the following actions
  • Serum albumin <3.5 g/dL or reduced by ≥0.5 g/dL from albumin before dosing initiation of current cycle: Administer albumin 25g IV (q12h or more frequently) until serum albumin ≥3.5 g/dL AND ≤0.5 g/dL lower than albumin before dosing initiation of the current cycle
  • Predose body weight increased by ≥1.5 kg over previous day’s predose weight: Administer albumin 25g IV (q12h or more frequently) and manage fluid status as clinically indicated (eg, IV fluids and vasopressors if hypotensive and diuretics if normotensive and hypertensive) until body weight increase has resolved
  • Edema, fluid overload, and/or hypotension: Administer albumin 25g IV (q12h or more frequently) until serum albumin ≥3.5 g/dL, methylprednisolone (or equivalent) 1 mg/kg/day IV, and aggressive management of fluid status and hypotension if present (may include IV fluids and/or diuretics or other blood pressure management) until CLS sign/symptom resolves or as clinically indicated

Dosing Considerations

Before first dose in Cycle 1, ensure patient has adequate cardiac function and serum albumin ≥3.2 g/dL

During treatment, monitor vital signs and check albumin, ALT/AST, and creatinine before preparing each dose and as clinically indicsated

Conduct pregnancy testing in females of reproductive potential within 7 days before initiating treatment

Blastic Plasmacytoid Dendritic Cell Neoplasm

CD123-directed cytotoxin for treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN)

<2 years: Safety and efficacy not established

≥2 years

• Each cycle is 21 days
• Premedicate with H1-histamine antagonist, H2- histamine antagonist, corticosteroid, and acetaminophen 60 minutes before each dose
• Days 1-5: 12 mcg/kg IV qDay
• Continue treatment until disease progression or unacceptable toxicity
• Dosing period may be extended for dose delays up to Day 10 of the cycle

Dosage Modifications

Dosage modifications based on parameter and severity criteria

• ALT or AST increase >5x ULN: Withhold until AST/ALT ≤2.5x ULN
• Serum creatinine >1.8 mg/dL or CrCl ≤60 mL/min: Withhold until serum creatinine ≤1.8 mg/dL or CrCl ≥60 mL/min
• Systolic blood pressure (SBP) ≥160 mm Hg or ≤80 mm Hg: Withhold until SBP <160 mm Hg or >80 mm Hg
• Heart rate (HR) ≥130 bpm or ≤40 bpm: Withhold until HR is <130 bpm or >40 bpm
• Body temperature ≥38°C: Withhold until body temperature <38°C

• Hypersensitivity reactions

  • Mild or moderate: Withhold until any mild or moderate hypersensitivity reaction resolves; resume at the same infusion rate
  • Severe or life-threatening: Discontinue permanently

Capillary leak syndrome (CLS) guidelines

• Before first dose in Cycle 1

  • Serum albumin <3.2 g/dL: Administer when serum albumin ≥3.2 g/dL

• During treatment

  • Interrupt dosing until relevant CLS sign/symptom resolves while implementing the following actions
  • Serum albumin <3.5 g/dL or reduced by ≥0.5 g/dL from albumin before dosing initiation of current cycle: Administer albumin 25g IV (q12h or more frequently) until serum albumin ≥3.5 g/dL AND ≤0.5 g/dL lower than albumin before dosing initiation of the current cycle
  • Predose body weight increased by ≥1.5 kg over previous day’s predose weight: Administer albumin 25g IV (q12h or more frequently) and manage fluid status as clinically indicated (eg, IV fluids and vasopressors if hypotensive and diuretics if normotensive and hypertensive) until body weight increase has resolved
  • Edema, fluid overload, and/or hypotension: Administer albumin 25g IV (q12h or more frequently) until serum albumin ≥3.5 g/dL, methylprednisolone (or equivalent) 1 mg/kg/day IV, and aggressive management of fluid status and hypotension if present (may include IV fluids and/or diuretics or other blood pressure management) until CLS sign/symptom resolves or as clinically indicated

Dosing Considerations

Before first dose in Cycle 1, ensure patient has adequate cardiac function and serum albumin ≥3.2 g/dL

During treatment, monitor vital signs and check albumin, ALT/AST, and creatinine before preparing each dose and as clinically indicated

Conduct pregnancy testing in females of reproductive potential within 7 days before initiating treatment

Of the 94 patients who received tagraxofusp at labeled dose in STML-401-0114, 23% were ≥75 years; older patients experienced a higher incidence of altered mental status (including confusional state, delirium, mental status changes, dementia, and encephalopathy) than younger patients

Contraindicated (0)

Serious - Use Alternative (0)

Monitor Closely (1)

• siponimod

  siponimod and tagraxofusp both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

Minor (0)

• siponimod

  Monitor Closely (1)siponimod and tagraxofusp both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.