Moxetumomab pasudotox is a CD22-directed antibody-drug conjugate approved for the treatment of adult patients with relapsed or refractory hairy cell leukemia who received at least 2 prior systemic therapies, including treatment with a purine nucleoside analog. Moxetumomab pasudotox was voluntarily withdrawn from the market in August 2023 due to low usage.
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.
Intravenous Administration
-Moxetumomab pasudotox is available as a 1-mg lyophilized, single-use vial.
-Do NOT use the supplied IV solution stabilizer to reconstitute the moxetumomab pasudotox vial or to flush the line after drug administration.
-Premedicate all patients with an antihistamine, acetaminophen, and a histamine-2 receptor antagonist prior to each infusion; stop the infusion if a severe infusion-related reaction occurs.
-Administer IV fluids prior to and after each infusion.
Reconstitution:
-Calculate the required dose and number of vials and then add 1.1 mL of sterile water for injection to each 1-mg lyophilized vial for a final concentration of 1 mg/mL; do not round the dose down for partial vials.
-Direct the diluent along the walls of the vial and not directly on the lyophilized contents.
-Gently swirl the vial until the reconstituted solution is clear to slightly opalescent, colorless to slightly yellow, and with no visible particles.
-The reconstituted vials do not contain preservatives so further dilute the vial(s) immediately.
Dilution:
-Add 1 mL of the supplied IV solution stabilizer to an infusion bag containing 50 mL of 0.9% sodium chloride injection; only use 1 vial of the IV solution stabilizer per administration of moxetumomab pasudotox.
-Gently invert the infusion bag to mix; do not shake.
-Withdraw the appropriate amount (mL) from the moxetumomab pasudotox 1 mg/mL vials for the calculated dose (use actual body weight) and add it to the infusion bag.
-Gently invert the infusion bag of the final diluted admixture to mix; do not shake.
-Discard any unused portion left in the moxetumomab pasudotox or IV solution stabilizer vials.
-Storage after dilution: store at room temperature (20 to 25 degrees C; 68 to 77 degrees F) for up to 4 hours or refrigerated (2 to 8 degrees C; 36 to 46 degrees F) for up to 24 hours; protect from light and do not freeze or shake. The moxetumomab pasudotox dose should be given within 24 hours of reconstitution.
Intravenous (IV) Infusion
-Allow refrigerated diluted admixtures to warm to room temperature for no more than 4 hours prior to administration.
-Administer the diluted admixture as an IV infusion over 30 minutes; protect from light.
-Flush the IV line with 0.9% sodium chloride injection at the same rate as the infusion to ensure the full dose is delivered.
-Do not mix or administer moxetumomab pasudotox with other medicinal products.
Gastrointestinal adverse events including nausea (35%; grade 3, 2.5%), constipation (23%), and diarrhea (21%) were reported in patients with relapsed or refractory hairy-cell leukemia who received moxetumomab pasudotox in a nonrandomized clinical trial (n = 80). Following the infusion, an oral corticosteroid (e.g., dexamethasone 4 mg) is recommended to decrease the incidence of nausea and vomiting.
Fever was reported in 31% of patients with relapsed or refractory hairy-cell leukemia who received moxetumomab pasudotox in a nonrandomized clinical trial (n = 80); grade 3 fever occurred in 1.3% of patients.
Fatigue was reported in 34% of patients with relapsed or refractory hairy-cell leukemia who received moxetumomab pasudotox in a nonrandomized clinical trial (n = 80).
Headache was reported in 33% of patients with relapsed or refractory hairy-cell leukemia who received moxetumomab pasudotox in a nonrandomized clinical trial (n = 80).
Monitor complete blood counts prior to each moxetumomab pasudotox dose, on day 8, and mid-cycle of each treatment cycle. Hematologic adverse events including anemia (21%; grade 3, 10%), decreased hemoglobin levels (43%; grade 3, 15%), neutropenia/decreased neutrophil count (41%; grade 3 and 4, 31%), and thrombocytopenia/decreased platelet count (21%; grade 3 and 4, 14.8%) were reported in patients with relapsed or refractory hairy-cell leukemia who received moxetumomab pasudotox in a nonrandomized clinical trial (n = 80).
Monitor blood chemistries including liver function tests and lactate dehydrogenase (LDH) prior to each moxetumomab pasudotox dose, on day 8, and mid-cycle of each treatment cycle. Elevated hepatic enzymes including increased AST (55%; grade 3, 1.3%) and ALT (65%; grade 3, 3.8%) levels, hypoalbuminemia (64%; grade 3, 1.3%), hyperbilirubinemia/increased bilirubin level (30%; grade 3, 1.3%), increased gamma-glutamyltransferase (GGT) level (25%), and increased alkaline phosphatase level (20%) were reported in patients with relapsed or refractory hairy-cell leukemia who received moxetumomab pasudotox in a nonrandomized clinical trial (n = 80).
Monitor fluid balance prior to each moxetumomab pasudotox dose, on day 8, and mid-cycle of each treatment cycle. Fluid retention was reported in 63% of patients with relapsed or refractory hairy-cell leukemia who received moxetumomab pasudotox in a nonrandomized clinical trial (n = 80); grade 3 fluid retention occurred in 1.3% of patients. Diuretic therapy was required in 29% of patients who had fluid retention. The term fluid retention included edema (5%), peripheral edema (39%), face edema (14%), abdominal distension (13%), weight gain (8%), pleural effusion (6%), peripheral swelling (5%), localized edema (3.8%), ascites (1.3%), fluid overload (1.3%), and pericardial effusion (1.3%).
Ocular adverse events including blurred vision (9%), xerophthalmia (8%), cataracts (5%), ocular pain or discomfort (4%), ocular swelling/periorbital edema (4%), conjunctivitis (1.3%), conjunctival/ocular hemorrhage (1.3%), and ocular discharge (1.3%) were reported in patients with relapsed or refractory hairy-cell leukemia who received moxetumomab pasudotox in a nonrandomized clinical trial (n = 80).
In pooled results from a combined safety database (n = 129), capillary leak syndrome (CLS) was reported in 34% of patients who received moxetumomab pasudotox, including grade 3 (1.6%) or grade 4 (2%) CLS. Features of CLS may include symptoms of fluid overload and hemoconcentration. Monitor patient weight and blood pressure prior to each infusion and then as clinically indicated during therapy. Evaluate patients who experience weight gain (increase of 2.5 kg or 5% or more weight increase from day 1 of current cycle) and hypotension for peripheral edema, respiratory symptoms (e.g., dyspnea, cough), and laboratory changes such as hypoalbuminemia, elevated hematocrit, leukocytosis, and thrombocytosis. Check for a decrease in oxygen saturation and evidence or pulmonary edema or serosal effusions (e.g., pericardial effusion, pleural effusion) if CLS is suspected. Immediately start appropriate supportive measures including oral or IV corticosteroids in patients who develop grade 2 or higher CLS; monitor weight, albumin levels, and blood pressure until resolution. Hospitalization may be necessary in some cases. Therapy interruption or discontinuation is necessary in patients who develop grade 2 or higher CLS. Most cases of CLS occurred within 8 days (range, 1 to 19 days) from the start of a treatment cycle; the median time to toxicity resolution was 12 days (range, 1 to 53 days).
In pooled results from a combined safety database (n = 129), hemolytic-uremic syndrome (HUS) was reported in 7% of patients who received moxetumomab pasudotox, including grade 3 (3%) or grade 4 (0.8%) HUS. Features of HUS include a triad of microangiopathic hemolytic anemia, thrombocytopenia, and progressive renal failure. In one study, patients who had a platelet count of 100,000 cells/mm3 or greater received thromboprophylaxis with aspirin on days 1 to 8 of each cycle of moxetumomab pasudotox therapy. Administer IV fluids prior to and following each infusion; maintain oral hydration on days 1 to 8 of each cycle. Monitor blood chemistries (e.g., LFTs, serum creatinine, LDH) and complete blood counts prior to each moxetumomab pasudotox dose, on day 8, and mid-cycle of each treatment cycle; evaluate patients for signs and symptoms of thrombosis. If HUS is suspected, check serum LDH level, indirect bilirubin level, and a blood smear for schistocytes (indicates hemolysis); initiate supportive measures including fluid repletion and hemodynamic monitoring. Hospitalization may be necessary. Treatment delay may result in progressive renal failure requiring dialysis. Discontinue therapy in patients who develop HUS; monitor laboratory parameters until resolution. Most cases of HUS occurred within 9 days (range, 1 to 16 days) from the start of a treatment cycle; the median time to toxicity resolution was 11.5 days (range, 2 to 44 days).
Antibody formation (detected by electrochemiluminescent assay) was reported in 59% of patients who received moxetumomab pasudotox (n = 76) in a clinical trial. Patients who tested positive for anti-moxetumomab pasudotox antibodies had decreased systemic moxetumomab pasudotox concentrations. Neutralizing antibodies were detected in 67 of 70 patients (96%) who had anti-moxetumomab pasudotox antibodies at any point during the study.
Monitor renal function prior to each dose of moxetumomab pasudotox and then as clinically indicated during therapy. Therapy interruption may be necessary in patients who develop renal impairment. In pooled results from a combined safety database (n = 129), nephrotoxicity was reported in 26% of patients who received moxetumomab pasudotox, including acute kidney injury (2.3%; grade 3, 1.6%), renal failure (unspecified) (2.3%), renal impairment (1.6%), increased serum creatinine (SCr) level (17%), and proteinuria (8%). Increased SCr levels (by 2 or more grades from baseline) occurred in 22% of patients and grade 3 increased SCr levels were reported in 1.6% of patients; 5% of patients had SCr levels that remained elevated at 1.5- to 3-times the upper limit of normal at the end of moxetumomab pasudotox treatment. Increased SCr level was reported in 96% of patients with relapsed or refractory hairy-cell leukemia who received moxetumomab pasudotox in a nonrandomized clinical trial (n = 80); grade 3 increased SCr level occurred in 2.5% of patients.
Infusion-related reactions were reported in 50% of patients with relapsed or refractory hairy-cell leukemia who received moxetumomab pasudotox in a nonrandomized clinical trial (n = 80); grade 3 infusion reactions occurred in 3.8% of patients. The most commonly reported reactions included nausea (15%), fever (14%), chills (14%), vomiting (11%), headache (9%), and infusion-related reaction (9%). Other adverse events that may be associated with an infusion-related reaction are cough, dizziness, dyspnea, feeling hot, flushing, hypertension, hypotension, myalgia, sinus tachycardia, tachycardia, or wheezing. Premedicate all patients with an antihistamine (e.g., hydroxyzine or diphenhydramine), acetaminophen, and a histamine-2 receptor antagonist (e.g., ranitidine, famotidine, or cimetidine) at 30 to 90 minutes prior to each infusion. Following the infusion, oral antihistamines and antipyretics may be continued for up to 24 hours. If a severe infusion-related reaction occurs, stop the infusion and institute medical management. Give oral or IV corticosteroids 30 minutes prior to resuming therapy and prior to each infusion thereafter.
Monitor serum electrolytes prior to each moxetumomab pasudotox dose, on day 8, and mid-cycle of each treatment cycle. In pooled results from a combined safety database (n = 129), electrolyte abnormalities were reported in 57% of patients who received moxetumomab pasudotox including grade 3 (14%) and grade 4 (0.8) electrolyte abnormalities. Hypocalcemia occurred in 25% of moxetumomab-treated patients. Additionally, 37% of patients had electrolyte abnormalities in the same treatment cycle with capillary leak syndrome, hemolytic-uremic syndrome, fluid retention, or renal toxicity. Hypocalcemia (54%), hypophosphatemia (53%; grade 3, 14%), hyponatremia (41%; grade 3, 8.8%), hypokalemia (25%; grade 3, 2.6%), hypomagnesemia (23%; grade 3, 1.3%), and hyperuricemia (21%; grade 4, 2.5%) were reported in patients with relapsed or refractory hairy-cell leukemia who received moxetumomab pasudotox in a nonrandomized clinical trial (n = 80).
Severe capillary leak syndrome (CLS) has been reported with moxetumomab pasudotox use; most cases occur within 8 days (range, 1 to 19 days) from the start of a treatment cycle. Monitor patient weight and blood pressure prior to each infusion and then as clinically indicated during therapy. Evaluate patients for signs (e.g., hypoalbuminemia, elevated hematocrit, leukocytosis, and thrombocytosis) and symptoms (e.g., weight gain (increase of 2.5 kg or 5% or more weight increase from day 1 of current cycle), hypotension, peripheral edema, dyspnea or cough, or pulmonary edema or serosal effusions) of CLS. Immediately start appropriate supportive measures including oral or IV corticosteroids in patients who develop grade 2 or higher CLS; monitor weight, albumin levels, and blood pressure until resolution. Therapy interruption or discontinuation is necessary in patients who develop grade 2 or higher CLS.
Avoid moxetumomab pasudotox use in patients who have a history of severe thrombotic microangiopathy (TMA) or hemolytic-uremic syndrome (HUS). Severe HUS has been reported with moxetumomab use; most cases occur within 9 days (range, 1 to 16 days) from the start of a treatment cycle. Administer IV fluids prior to and following each moxetumomab pasudotox infusion; maintain oral hydration on days 1 to 8 of each cycle. Consider low-dose aspirin on days 1 to 8 of each therapy cycle. Monitor blood chemistries (e.g., LFTs, serum creatinine, LDH) and complete blood counts prior to each moxetumomab pasudotox dose, on day 8, and mid-cycle of each treatment cycle; evaluate patients for signs and symptoms of thrombosis. If HUS is suspected, initiate supportive measures including fluid repletion and hemodynamic monitoring; hospitalization may be necessary. Discontinue therapy in patients who develop HUS; monitor laboratory parameters until resolution.
Avoid moxetumomab pasudotox use in patients with severe renal impairment (creatinine clearance of 29 mL/min or less). Geriatric patients (aged 65 years and older) and patients with hemolytic-uremic syndrome or baseline renal impairment may have a greater risk of developing worsening renal function following moxetumomab pasudotox treatment. Monitor renal function prior to each dose of moxetumomab pasudotox and then as clinically indicated during therapy. Therapy interruption may be necessary in patients who develop renal impairment. Drug discontinuation (23% vs. 7%) and renal toxicity (40% vs. 20%) occurred more often in patients 65 years of age or older who received moxetumomab pasudotox compared with patients younger than 65 years of age.
Infusion-related reactions have been reported with moxetumomab pasudotox use; these reactions may occur during any cycle of therapy. Premedicate all patients with an antihistamine (e.g., hydroxyzine or diphenhydramine), acetaminophen, and a histamine-2 receptor antagonist (e.g., ranitidine, famotidine, or cimetidine) at 30 to 90 minutes prior to each infusion. Following the infusion, oral antihistamines and antipyretics may be continued for up to 24 hours. If a severe infusion-related reaction occurs, stop the infusion and institute medical management. Give oral or IV corticosteroids 30 minutes prior to resuming therapy and prior to each infusion thereafter.
Monitor fluid balance and serum electrolytes to avoid fluid overload and/or electrolyte imbalance prior to each moxetumomab pasudotox dose, on day 8, and mid-cycle of each treatment cycle.
Moxetumomab pasudotox may cause fetal harm when administered during pregnancy, based on its mechanism of action. Females of reproductive potential should be advised to avoid becoming pregnant while receiving moxetumomab pasudotox. If a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus.
Counsel patients about the reproductive risk and contraception requirements during moxetumomab pasudotox treatment. Pregnancy testing should be performed prior to starting moxetumomab in female patients of reproductive potential. These patients should use effective contraception and avoid pregnancy during and for at least 30 days after moxetumomab pasudotox therapy. Women who become pregnant while receiving moxetumomab pasudotox should be apprised of the potential hazard to the fetus.
Discontinue breast-feeding during moxetumomab pasudotox therapy. It is not known if moxetumomab is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.
Moxetumomab pasudotox was voluntarily withdrawn from the market in August 2023 due to low usage.
For the treatment of hairy-cell leukemia*:
NOTE: Moxetumomab pasudotox has been designated by the FDA as an orphan drug for the treatment of hairy-cell leukemia.
-for the treatment of relapsed or refractory hairy-cell leukemia in patients who have received at least 2 prior systemic therapies, including treatment with a purine nucleoside analog*:
Intravenous dosage:
Adults: Dosage not established.
Maximum Dosage Limits:
-Adults
Dosage not established.
-Geriatric
Dosage not established.
Patients with Hepatic Impairment Dosing
Dosage not established.
Patients with Renal Impairment Dosing
Dosage not established.
*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.
Moxetumomab pasudotox is a CD22-directed antibody-drug conjugate. It is a recombinant immunotoxin composed of an immunoglobulin light chain variable domain and a heavy chain variable domain genetically fused to a truncated form of Pseudomonas exotoxin PE38. CD22 is expressed on the cell surface of B-cells. Hairy-cell leukemia is a rare B-cell malignancy with high CD22 expression. Moxetumomab pasudotox binds to CD22 and is internalized into the cell which results in ADP-ribosylation of elongation factor 2, inhibition of protein synthesis, and apoptotic cell death.
Moxetumomab pasudotox is administered intravenously. In a population pharmacokinetic analysis, it had a mean volume of distribution of 6.5 +/- 2.4 L, a mean elimination half-life of 1.4 +/- 0.35 hours (range, 0.8 to 1.8 hours), and estimated mean systemic clearance values of 25 +/- 29 L/hour after the first dose of cycle 1 and 4 +/- 4.4 L/hour after subsequent dosing. The metabolism of moxetumomab pasudotox is not known; however, other proteins undergo proteolytic degradation to form small peptides and amino acids via catabolic pathways.
-Route-Specific Pharmacokinetics
Intravenous Route
The mean steady-state Cmax and AUC values were 379 +/- 262 ng/mL (range, 20 to 862 ng/mL) and 626 +/- 610 ng X hour/mL (range, 5 to 1,960 ng X hour/mL), respectively, in patients with hairy-cell leukemia who received moxetumomab pasudotox at the recommended dosage; no systemic accumulation was observed.
-Special Populations
Hepatic Impairment
Mild hepatic impairment (total bilirubin level at or less than the upper limit of normal (ULN) and an AST level greater than the ULN OR a total bilirubin level greater than 1 to 1.5-times the ULN and any AST level) had no clinically significant impact on the pharmacokinetic (PK) parameters of moxetumomab pasudotox in a population PK analysis. There are insufficient PK data in patients with moderate and severe hepatic impairment (total bilirubin level greater than 1.5-times the ULN).
Renal Impairment
Mild (creatinine clearance (CrCl), 60 to 89 mL/min) and moderate (CrCl, 30 to 59 mL/min) renal impairment had no clinically significant impact on the pharmacokinetic (PK) parameters of moxetumomab pasudotox in a population PK analysis. There are insufficient PK data in patients with severe renal impairment (CrCl, 29 mL/min or less).
Geriatric
Age (range, 36 to 84 years) had no clinically significant impact on the pharmacokinetic (PK) parameters of moxetumomab pasudotox in a population PK analysis.
Gender Differences
Gender had no clinically significant impact on the pharmacokinetic (PK) parameters of moxetumomab pasudotox in a population PK analysis.
Ethnic Differences
Ethnicity had no clinically significant impact on the pharmacokinetic (PK) parameters of moxetumomab pasudotox in a population PK analysis.
Obesity
Weight (range, 42 to 152 kg) had no clinically significant impact on the pharmacokinetic (PK) parameters of moxetumomab pasudotox in a population PK analysis.
Other
Anti-Product Antibody (ADA) Formation
The presence of ADA post-baseline resulted in a statistically significant lower pharmacokinetic exposure of moxetumomab pasudotox at therapy cycle 3 and beyond in patients who were ADA-positive with high titers.