Tagraxofusp

Tagraxofusp is used for: Blastic Plasmacytoid Dendritic Cell Neoplasm

Blastic Plasmacytoid Dendritic Cell Neoplasm CD123-directed cytotoxin for treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) Each cycle is 21 days 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

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 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

IV Preparation Prior to dose preparation, thaw at room temperature, 15-25°C (59-77°F), for 15-30 min in original carton, and verify thaw visually; may be held at room temperature for ~1 hr prior to dosage preparation Do not force-thaw; do not refreeze vial once thawed Visually inspect vial for particulate matter and discoloration prior to administration Thawed drug appears as a clear, colorless liquid that may contain a few white-to-translucent particles Prepare 10 ml of tagraxofusp 100 mcg/mL Transfer 9 mL of 0.9% NaCl to an empty sterile 10-mL vial Gently swirl drug vial to mix contents, remove cap, and withdraw 1 mL of thawed drug Transfer 1 mL into sterile 10-mL vial containing 0.9% NaCl Gently invert vial ?3x to mix contents; do not shake vigorously Final concentration of diluted solution is 100 mcg/mL Prepare infusion set Calculate and draw up required volume of diluted solution (100 mcg/mL) according to patient’s weight If dose requires >10 mL, prepare a second vial of diluted solution Refer to prescribing information for further details on infusion set setup Do not reuse excess diluted drug solution; discard any excess material immediately following infusion Premedication Premedicate with an H1-histamine antagonist (eg, diphenhydramine), H2-histamine antagonist (eg, ranitidine), corticosteroid (eg, 50 mg IV methylprednisolone or equivalent) and acetaminophen (or paracetamol) ~60 min prior to each infusion IV Administration Administration setting Cycle 1: Administer in an inpatient setting with patient observation through ?24 hr after last infusion Subsequent cycles: Administer in an inpatient setting or a suitable outpatient ambulatory care setting equipped with appropriate monitoring for patients with hematopoietic malignancies undergoing treatment Establish IV access and maintain with sterile 0.9% NaCl Administer prepared dose via infusion syringe pump over 15 min Total infusion time is controlled using a syringe pump to deliver entire dose and saline flush over 15 minutes After infusion set setup: Administer within 4 hr at room temperature Refer to the prescribing information for infusion pump set up

Capillary leak syndrome reported; interrupt dose and manage according to presenting symptoms May cause severe hypersensitivity reactions (eg, rash, pruritus, stomatitis, wheezing); monitor for hypersensitivity reactions during treatment; interrupt infusion and provide supportive care as needed if a hypersensitivity reaction occurs Treatment was associated with elevations in liver enzymes; monitor AST/ALT prior to each infusion

Pregnancy Based on its mechanism of action, therapy has potential for adverse effects on embryo-fetal development Data are not available on use in pregnant women to inform a drug-associated risk of adverse developmental outcomes Advise pregnant women of potential risks to the fetus Conduct pregnancy testing in females of reproductive potential within 7 days before initiating treatment Contraception Advise females to use acceptable contraceptive methods during treatment and for at least 1 week after last dose Lactation No data are available on the presence of drug in human milk, the effects on the breastfed child, or the effects on milk production Because of potential for serious adverse reactions in breastfed children from tagraxofusp, breastfeeding is not recommended during treatment and for 1 week after last dose

Side effects of Tagraxofusp : >10% (All Grades) Glucose increased (87%) ALT increased (82%) AST increased (79%) Albumin decreased (77%) Platelets decreased (67%) Hemoglobin decreased (60%) Calcium decreased (57%) Capillary leak syndrome (55%) Sodium decreased (50%) Nausea (49%) Fatigue (45%) Peripheral edema (43%) Pyrexia (43%) Neutrophils decreased (37%) Weight increased (31%) Phosphate decreased (30%) Chills (29%) Headache (29%) Hypotension (29%) Creatinine increased (27%) Alkaline phosphatase increased (26%) Decreased appetite (24%) Constipation (23%) Potassium increased (21%) Vomiting (21%) Diarrhea (20%) Magnesium decreased (20%) Dizziness (20%) Febrile neutropenia (20%) Back pain (20%) Dyspnea (19%) Tachycardia (17%) Insomnia (17%) Anxiety (15%) Hypertension (15%) Cough (14%) Magnesium increased (14%) Bilirubin increased (14%) Epistaxis (14%) Oropharyngeal pain (12%) Anxiety (15%) Confusional state (11%) Glucose decreased (11%) >10% (Grade 3 or 4) Platelets decreased (53%) AST increased (37%) Hemoglobin decreased (35%) Neutrophils decreased (31%) ALT increase (30%) Glucose increased (20%) Febrile neutropenia (18%) Phosphate decreased (11%)

CD123-directed cytotoxin, which is a fusion protein composed of a recombinant human interleukin 3 and truncated diphtheria toxin Inhibits protein synthesis and causes cell death in CD123-expressing cells