Tagraxofusp-erzs is a CD123-directed cytotoxin that is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm in adult and pediatric patients 2 years of age and older. Capillary leak syndrome has been reported with tagraxofusp therapy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Emetic Risk
-Low
-Administer routine antiemetic prophylaxis prior to treatment.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. After thawing, the tagraxofusp solution is a clear, colorless liquid that may contain a few white to translucent particles.
Intravenous Administration
-Tagraxofusp-erzs is available as a 1,000 mcg/mL solution in a single-dose vial.
-Premedication with acetaminophen, H1-histamine antagonist, H2-histamine antagonist, and a corticosteroid prior to each dose is recommended; observe patients during and for at least 4 hours after the end of the infusion for symptoms of a hypersensitivity reaction.
Thaw Vial(s):
-Calculate the required dose of tagraxofusp; 2 vials will be needed if the dose exceeds 1,000 mcg.
-Prior to dilution, thaw vial(s) at room temperature between 15 and 25 degrees C (59 and 77 degrees F) for 15 to 30 minutes in the original carton.
-Storage of thawed vial(s): store at room temperature for up to about 1 hour prior to dose preparation; do not re-freeze.
Dilution:
-Using a sterile 10-mL syringe, transfer 9 mL of 0.9% sodium chloride injection to an empty sterile 10-mL vial.
-After swirling the tagraxofusp vial gently, withdraw 1 mL of thawed tagraxofusp from the product vial using a 1-mL syringe and transfer to the 10-mL vial containing 0.9% sodium chloride injection for a final concentration of 100 mcg/mL.
-Invert the 100 mcg/mL solution gently at least 3 times to mix the contents; do not shake vigorously.
-Repeat these steps if more than 1 vial of the drug is required for a patient dose.
Infusion-Set Preparation:
-Calculate and draw up the required volume of the 100 mcg/mL solution into a new syringe to make the patient dose; label the tagraxofusp syringe.
-Prepare a separate syringe with at least 3 mL of 0.9% sodium chloride injection; label the saline flush syringe.
-Connect the saline flush syringe to 1 arm of a mini-bifuse Y-connector and connect the tagraxofusp syringe to the other arm; ensure the clamps are closed.
-Connect the terminal end of the Y-connector to microbore tubing; remove the cap from the supply side of a 0.2-micron polyethersulfone in-line filter and attach it to the terminal end of the microbore tubing.
-Unclamp the arm of the Y-connector connected to the saline flush syringe and prime the Y-connector up to the intersection; do not prime the full infusion set with saline.
-Re-clamp the Y-connector line on the saline flush arm.
-Remove the cap on the terminal end of the 0.2-micron filter and set it aside. Unclamp the arm of the Y-connector connected to the tagraxofusp syringe and prime the entire infusion set (including the filter).
-Recap the filter and re-clamp the Y-connector line on the tagraxofusp side.
-Storage of syringe: use within 4 hours of dilution; keep at room temperature.
Intravenous (IV) Syringe:
-Maintain venous access with 0.9% sodium chloride injection.
-Administer the prepared tagraxofusp dose IV over 15 minutes via an infusion syringe pump; deliver the entire dose and saline flush over 15 minutes.
-Insert the tagraxofusp syringe into the syringe pump and open the clamp on the tagraxofusp side of the Y-connector and deliver the prepared dose.
-Once the tagraxofusp syringe has been emptied, remove it from the pump and place the saline flush syringe in the syringe pump.
-Open the clamp on the saline flush side of the Y-connector and resume infusion via the syringe pump at the pre-specified flow to push remaining tagraxofusp dose out of the infusion line to complete delivery.
Hypotension (25%; grade 3 or 4, 7%) and hypertension (14%; grade 3 or 4, 6%) were reported in adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122). Therapy interruption may be necessary in patients who develop hypotension or hypertension. Administer treatment or supportive care as required for hypotension (e.g., IV fluids, vasopressors).
Sinus tachycardia was reported in 17% of adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122). Therapy interruption may be necessary in patients who develop tachycardia or bradycardia.
Fever (43%) and chills (26%; grade 3 or 4, 1%) were reported in adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122). Therapy interruption may be necessary in patients who develop a fever.
Weight gain was reported in 31% of adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122). Therapy interruption may be necessary in patients who develop weight gain; administer albumin and manage fluid status as clinically indicated.
Hypoalbuminemia was reported in 72% (grade 3 or 4, 1%) of adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122). Evaluate serum albumin levels prior to each dose and as clinically indicated. Therapy interruption may be necessary in patients who develop hypoalbuminemia; administer albumin as indicated.
Peripheral edema was reported in 39% (grade 3 or 4, 1%) of adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122). Therapy interruption may be necessary in patients who develop edema or fluid overload; administer treatment or supportive care as required (e.g., albumin, diuretics).
Gastrointestinal adverse events including nausea (45%), constipation (24%), vomiting (19%), diarrhea (21%), and decreased appetite/anorexia (22%) were reported in adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122).
Fatigue was reported in 45% (grade 3 or 4, 7%) of adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122).
Headache (28%), and dizziness (21%) were reported in adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122).
Back pain (19%; grade 3 or 4, 2%) and extremity pain (10%; grade 3 or 4, 2%) were reported in adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122).
Respiratory adverse events including dyspnea (20%; grade 3 or 4, 3%) and cough (12%) were reported in adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122).
Epistaxis was reported in 12% (grade 3 or 4, 1%) of adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122).
Pruritus was reported in 10% of adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122).
Hematologic toxicity including decreased platelet count/thrombocytopenia (68%; grade 3 or 4, 49%), decreased hemoglobin level/anemia (61%; grade 3 or 4, 30%), decreased neutrophil count/neutropenia (38%; grade 3 or 4, 29%), and febrile neutropenia (19%; grade 3 or 4, 16%) were reported in adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122).
Hyperglycemia (89%; grade 3 or 4, 21%) and hypoglycemia (10%) were reported in adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122).
Electrolyte abnormalities including hypocalcemia (57%; grade 3 or 4, 2%), hyponatremia (52%; grade 3 or 4, 9%), hypokalemia (36%; grade 3 or 4, 6%), hypophosphatemia (32%; grade 3 or 4, 10%), hyperkalemia (20%; grade 3 or 4, 3%), hypomagnesemia (25%), and hypermagnesemia (13%; grade 3 or 4, 4%) were reported in adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122).
Hepatotoxicity has been reported with tagraxofusp therapy. Monitor liver function tests prior to each tagraxofusp dose. Therapy interruption may be necessary in patients who develop severe hepatotoxicity. Elevated hepatic enzymes including AST (76%; grade 3 or 4, 33%) and ALT (79%; grade 3 or 4, 26%) levels, increased alkaline phosphatase level (22%; grade 3 or 4, 1%), and hyperbilirubinemia (11%) were reported in adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122). Most patients experienced elevated liver enzymes in cycle 1 and toxicity was reversible following a dosage interruption.
Nephrotoxicity, specifically increased serum creatinine (Scr) level was reported in 26% of adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122). Monitor Scr level prior to each tagraxofusp dose. Therapy interruption may be necessary in patients who develop nephrotoxicity.
Capillary leak syndrome (CLS) has been reported with tagraxofusp therapy. Evaluate serum albumin levels prior to each dose and as clinically indicated. Monitor patients for signs or symptoms of CLS (e.g., tachycardia, fever) during tagraxofusp therapy. Therapy may need to be interrupted if a patient develops signs or symptoms of CLS; administer treatment or supportive care as required (e.g., albumin, vasopressors, steroids). CLS was reported in 53% (grade 3 or higher, 11%) of adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122). CLS-associated hypoalbuminemia, edema, weight gain, and hypotension occurred in 20% or greater of patients; 4 patients died due to CLS. The median time to CLS onset was 4 (range, 1 to 46) days; most patients experienced an event in cycle 1. CLS was defined as any event reported as CLS during tagraxofusp treatment or the occurrence of at least 2 of the following CLS manifestations within 7 days of each other: hypoalbuminemia (including albumin value less than 3 g/dL), edema (including weight increase of 5 kg or more), or hypotension (including systolic blood pressure less than 90 mmHg).
Hypersensitivity reaction was reported in 43% (grade 3 or 4, 7%) of adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122). Symptoms of hypersensitivity that occurred in 5% or greater of patients included rash, pruritus, and stomatitis. Premedicate patients with an H1-histamine antagonist (e.g., diphenhydramine), H2-histamine antagonist (e.g., famotidine), corticosteroid (e.g., methylprednisolone), and acetaminophen prior to each infusion. Administer the first cycle of therapy in the inpatient setting and observe patients for at least 24 hours after the last infusion; thereafter, monitor patients for signs of hypersensitivity reactions for a minimum of 4 hours following each infusion. If tagraxofusp is given in an ambulatory care setting after the first cycle; ensure that there is appropriate monitoring for patients with hematopoietic malignancies undergoing treatment. Therapy interruption or permanent discontinuation may be necessary in patients who develop a hypersensitivity reaction; administer treatment or supportive care as required.
Antibody formation occurred in 99% or less of evaluable patients who received tagraxofusp in clinical trials; 85% of evaluable patients developed neutralizing antibodies. Additionally, 68% of evaluable patients had anti-IL3 antibodies; most of these patients tested positive by therapy cycle 3. There was an increase in anti-drug antibody titers and a reduction in tagraxofusp concentrations in most plasma samples evaluated in therapy cycle 3.
Insomnia (16%) and anxiety (15%) were reported in adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122).
Tumor lysis syndrome (TLS) was reported in less than 10% of adult patients with newly-diagnosed or relapsed/refractory myeloid malignancies who received tagraxofusp in a single-arm clinical trial (n = 122).
Capillary leak syndrome (CLS) has been reported with tagraxofusp use; some cases were life-threatening or fatal. Verify that patients have adequate cardiac function and a serum albumin level of 3.2 g/dL or greater prior to administering the first dose in cycle 1, then evaluate serum albumin levels prior to each dose and as clinically indicated thereafter. Monitor patients for signs or symptoms of CLS (e.g., weight gain, edema, hypotension, tachycardia, fever) during tagraxofusp therapy. Therapy may need to be interrupted if a patient develops signs or symptoms of CLS; administer treatment or supportive care as required (e.g., albumin, vasopressors, steroids).
Severe hypersensitivity reactions (e.g., serious rash, pruritus, stomatitis) have been reported with tagraxofusp use. Premedicate patients with an H1-histamine antagonist (e.g., diphenhydramine), H2-histamine antagonist (e.g., famotidine), corticosteroid (e.g., methylprednisolone 50 mg IV or equivalent), and acetaminophen prior to each infusion. Administer the first cycle of therapy in the inpatient setting and observe patients for at least 24 hours after the last infusion; thereafter, monitor patients for signs of hypersensitivity reactions for a minimum of 4 hours following each infusion. If tagraxofusp is given in an ambulatory care setting after the first cycle; ensure that there is appropriate monitoring for patients with hematopoietic malignancies undergoing treatment. Therapy interruption or permanent discontinuation may be necessary in patients who develop a hypersensitivity reaction; administer treatment or supportive care as required.
Hepatotoxicity (e.g., elevated hepatic enzymes) has been reported with tagraxofusp; therefore, use caution in patients with pre-existing hepatic disease. Monitor liver function tests prior to each tagraxofusp infusion. Therapy interruption may be necessary in patients who develop severe hepatotoxicity.
Nephrotoxicity (e.g., increased serum creatinine (Scr) level) has been reported with tagraxofusp; therefore, use caution in patients with pre-existing renal impairment. Monitor Scr level prior to each tagraxofusp infusion. Therapy interruption may be necessary in patients who develop nephrotoxicity.
Increased rate of altered mental status (e.g., confusion, delirium, mental status changes, dementia, and encephalopathy) was observed in geriatric patients 75 years and older who received tagraxofusp compared with younger patients in a clinical trial.
Tagraxofusp may cause fetal harm when administered during pregnancy, based its mechanism of action. Females of reproductive potential should avoid becoming pregnant while taking tagraxofusp. Discuss the potential hazard to the fetus if a patient becomes pregnant while taking this drug.
Counsel patients about the reproductive risk and contraception requirements during tagraxofusp therapy. Pregnancy testing should be performed in women of reproductive potential within 7 days prior to initiating therapy. These women should use effective contraception during therapy and for 1 week after the final tagraxofusp dose.
It is not known if tagraxofusp is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Because there is a potential for adverse reactions in nursing infants from tagraxofusp, women should be advised against breast-feeding during tagraxofusp therapy and for 1 week after the last dose.
For the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN):
NOTE: The FDA has designated tagraxofusp-erzs as an orphan drug for the treatment of BPDCN.
Intravenous dosage:
Adults: 12 micrograms/kg IV once daily on days 1, 2, 3, 4, and 5 repeated every 21 days until disease progression. The dosing period may be extended for dose delays up to day 10 of the cycle. Verify that patients have adequate cardiac function and a serum albumin level of 3.2 g/dL or greater prior to administering the first dose in cycle 1. Premedicate patients with an H1-histamine antagonist (e.g., diphenhydramine), H2-histamine antagonist (e.g., famotidine), corticosteroid (e.g., methylprednisolone 50 mg IV or equivalent), and acetaminophen about 60 minutes prior to each infusion. Therapy interruption or discontinuation may be necessary in patients who develop severe toxicity. The primary endpoint of complete response (CR) or CR with residual skin abnormality (CRc) rate was 57% in adult patients with treatment-naive (n = 65) who received tagraxofusp at the recommended daily dose of 12 mcg/kg in a phase 1/2 trial. At a median follow-up time of 34 months, the median duration of CR/CRc was 24.9 months; the median overall survival (OS) time was 15.8 months and the estimated 24-month OS rate was 40%. Of patients who achieved a CR/CRc, 51% underwent an allogeneic (n = 13) or autologous (n = 6) stem-cell transplantation (SCT). The median OS was 38.4 (range, 3.4 to 58.1) months and the estimated 24-month OS rate was 66% in transplanted patients. The CR/CRc rate was 16% in adult patients with relapsed or refractory BPDCN (n = 19) who received tagraxofusp in this trial. At a median follow-up time of 33.5 months, the median OS time was 8.2 months; 1 patient achieved disease remission and underwent an allogeneic SCT.
Children 2 years and older and Adolescents: 12 micrograms/kg IV once daily on days 1, 2, 3, 4, and 5 repeated every 21 days until disease progression. The dosing period may be extended for dose delays up to day 10 of the cycle. Verify that patients have adequate cardiac function and a serum albumin level of 3.2 g/dL or greater prior to administering the first dose in cycle 1. Premedicate patients with an H1-histamine antagonist (e.g., diphenhydramine), H2-histamine antagonist (e.g., famotidine), corticosteroid (e.g., methylprednisolone), and acetaminophen about 60 minutes prior to each infusion. Therapy interruption or discontinuation may be necessary in patients who develop severe toxicity. Efficacy of tagraxofusp was established using data from 3 pediatric patients (2 adolescents and 1 child) with BPDCN and extrapolated data from adult BPDCN studies.
Therapeutic Drug Monitoring:
Management of Treatment-Related Toxicity
Hypersensitivity Reactions
Mild or moderate toxicity: Hold tagraxofusp; may resume therapy at the same infusion rate when symptoms resolve.
Severe or life-threatening toxicity: Permanently discontinue tagraxofusp.
Hypertension or Hypotension
Systolic blood pressure (SBP) of 160 mmHg or greater: Hold tagraxofusp; may resume therapy when SBP is less than 160 mmHg.
SBP of 80 mmHg or less: Hold tagraxofusp; may resume therapy when SBP is greater than 80 mmHg.
Tachycardia or Bradycardia
Heart rate of 130 beats per minute (bpm) or greater: Hold tagraxofusp; may resume therapy when the heart rate is less than 130 bpm.
Heart rate of 40 bpm or less: Hold tagraxofusp; may resume therapy when the heart rate is greater than 40 bpm.
Fever
Body temperature of 38 degrees C or higher: Hold tagraxofusp; may resume therapy when body temperature is less than 38 degrees C.
Management of Capillary Leak Syndrome (CLS)
NOTE: If all CLS signs/symptoms resolve and the patient does not require measures to treat hemodynamic instability, tagraxofusp therapy may resume in the same cycle; otherwise, hold tagraxofusp for the remainder of the cycle and resume in the next cycle only if all CLS signs/symptoms have resolved and the patient is hemodynamically stable.
Hypoalbuminemia
Serum albumin level less than 3.2 g/dL prior to the first cycle: Do not administer tagraxofusp until the serum albumin level is 3.2 g/dL or greater.
Serum albumin level less than 3.5 g/dL OR serum albumin level reduced by 0.5 g/dL or greater from value measured prior to the current cycle of therapy: Hold tagraxofusp; administer albumin 25 g IV every 12 hours (or more frequently) until the serum albumin level is 3.5 g/dL or greater AND not more than 0.5 g/dL lower than the value measured prior to the current cycle of therapy.
Weight Gain
Pre-dose body weight increased by 1.5 kg or more over the previous day's pre-dose weight: Hold tagraxofusp; administer albumin 25 g IV every 12 hours (or more frequently) and manage fluid status as clinically indicated (e.g., IV fluids, vasopressors, diuretics) until the body weight increase is resolved to less than 1.5 kg from the previous day's pre-dose weight.
Edema, Fluid Overload, and/or Hypotension
Hold tagraxofusp. Administer albumin 25 g IV every 12 hours (or more frequently) until serum albumin level is 3.5 g/dL or greater; give methylprednisolone 1 mg/kg IV (or an equivalent) daily until resolution of CLS signs/symptoms or as clinically indicated, and manage hypotension (if present) and fluid status (e.g., IV fluids, vasopressors, diuretics) until resolution of CLS signs/symptoms or as clinically indicated.
Maximum Dosage Limits:
-Adults
12 micrograms/kg IV daily for 5 days repeated every 21 days.
-Geriatric
12 micrograms/kg IV daily for 5 days repeated every 21 days.
-Adolescents
12 micrograms/kg IV daily for 5 days repeated every 21 days.
-Children
2 years of age or older: 12 micrograms/kg IV daily for 5 days repeated every 21 days.
Less than 2 years: Safety and efficacy not established.
-Infants
Safety and efficacy not established.
-Neonates
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in patients with baseline hepatic impairment are not available; it appears that no dosage adjustments are needed.
Treatment-Related Hepatotoxicity
AST or ALT level greater than 5-times the upper limit of normal (ULN): Hold tagraxofusp; may resume therapy when transaminase levels decrease to 2.5-times the ULN or less.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in patients with baseline renal impairment are not available; it appears that no dosage adjustments are needed.
Treatment-Related Nephrotoxicity
Serum creatinine (Scr) level greater than 1.8 mg/dL or creatinine clearance (CrCl) of less than 60 mL/min: Hold tagraxofusp; may resume therapy when the Scr level is 1.8 mg/dL or less or the CrCl is 60 mL/min or greater.
*non-FDA-approved indication
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Tagraxofusp-erzs is a CD123-directed cytotoxin. Tagraxofusp consists of a cytotoxic agent, truncated diphtheria toxin (DT), attached to a recombinant fusion protein, IL3. The IL3 domain binds to its natural receptor, DT is released into the cytosol and causes protein synthesis inhibition and cell death in CD123-expressing cells. Blastic plasmacytoid dendritic cell neoplasm blast cells have high CD123 or interleukin-3 receptor (IL3)-alpha surface expression.
Tagraxofusp-erzs is administered intravenously (IV). The mean volume of distribution was 5.1 L (standard deviation (SD), 1.9 L), the mean terminal half-life was 0.7 hours (SD, 0.3 hours), and the mean clearance was 7.1 L/hour (SD, 7.2 L/hour) in patients with blastic plasmacytoid dendritic cell neoplasm who received a single infusion of tagraxofusp 12 mcg/kg IV over 15 minutes.
-Route-Specific Pharmacokinetics
Intravenous Route
Following a single infusion of tagraxofusp 12 mcg/kg IV over 15 minutes, the mean Cmax and AUC values were 162 mcg/L (standard deviation (SD), 58.1 mcg/L) and 231 mcg X hour/L (SD, 123 mcg X hour/L), respectively, in patients with blastic plasmacytoid dendritic cell neoplasm.
-Special Populations
Hepatic Impairment
Mild (bilirubin level up to the upper limit of normal (ULN) and AST level greater than ULN, or a bilirubin level 1- to 1.5-times the ULN and any AST level) and moderate (bilirubin levels greater than 1.5- to 3-times the ULN and any AST level) hepatic impairment does not have a clinically significant impact on the pharmacokinetic (PK) parameters of tagraxofusp. It is not known if severe hepatic impairment (bilirubin level greater than 3-times the ULN and any AST level) affects the PK parameters of tagraxofusp.
Renal Impairment
Mild to moderate renal impairment (estimated glomerular filtration rate (eGFR) of 30 to 89 mL/min/1.73 m2) does not have a clinically significant impact on the pharmacokinetic (PK) parameters of tagraxofusp. It is not known if severe renal impairment (eGFR, 15 to 29 mL/min/1.73 m2) affects the PK parameters of tagraxofusp.
Geriatric
Age (range, 22 to 84 years) does not have a clinically significant impact on the pharmacokinetic parameters of tagraxofusp.
Gender Differences
Gender does not have a clinically significant impact on the pharmacokinetic parameters of tagraxofusp.
Obesity
Body weight (after adjusting dose by body weight) does not have a clinically significant impact on the pharmacokinetic parameters of tagraxofusp.
Other
Anti-Product Antibody Formation
There was an increase in anti-drug antibody titers and a reduction in free tagraxofusp concentrations in most plasma samples evaluated in therapy cycle 3. In patients with pre-existing anti-drug antibodies, the mean volume of distribution was 21.2 L (standard deviation (SD), 25.4 L), the mean clearance was 13.9 L/hour (SD, 19.4 L/hour), the mean Cmax value was 80 mcg/L (SD, 82.2 mcg/L), and the mean AUC value was 151 mcg X hour/L (SD, 89.2 mcg X hour/L) following tagraxofusp 12 mcg/kg IV over 15 minutes.