LUMOXITI

Antineoplastic Monoclonal Antibodies Targeting CD22
Antineoplastic Monoclonal Antibody-Drug Conjugates (ADCs)

Emetic Risk
Low
Administer routine antiemetic prophylaxis prior to treatment.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

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.[63547]

capillary leak syndrome / Early / 34.0-34.0
neutropenia / Delayed / 31.0-31.0
nephrotoxicity / Delayed / 26.0-26.0
anemia / Delayed / 10.0-15.0
thrombocytopenia / Delayed / 14.8-14.8
hypophosphatemia / Delayed / 14.0-14.0
hyponatremia / Delayed / 8.8-8.8
pleural effusion / Delayed / 6.0-6.0
elevated hepatic enzymes / Delayed / 1.3-3.8
hemolytic-uremic syndrome / Delayed / 3.8-3.8
infusion-related reactions / Rapid / 3.8-3.8
hypokalemia / Delayed / 2.6-2.6
nausea / Early / 2.5-2.5
hyperuricemia / Delayed / 2.5-2.5
renal failure (unspecified) / Delayed / 2.3-2.3
fever / Early / 1.3-1.3
hypoalbuminemia / Delayed / 1.3-1.3
hyperbilirubinemia / Delayed / 1.3-1.3
pericardial effusion / Delayed / 1.3-1.3
fluid retention / Delayed / 1.3-1.3
ocular hemorrhage / Delayed / 1.3-1.3
hypomagnesemia / Delayed / 1.3-1.3
pulmonary edema / Early / Incidence not known
thrombosis / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known

antibody formation / Delayed / 59.0-59.0
hypocalcemia / Delayed / 25.0-54.0
peripheral edema / Delayed / 39.0-39.0
constipation / Delayed / 23.0-23.0
blurred vision / Early / 9.0-9.0
proteinuria / Delayed / 8.0-8.0
edema / Delayed / 5.0-5.0
cataracts / Delayed / 5.0-5.0
ascites / Delayed / 1.3-1.3
conjunctivitis / Delayed / 1.3-1.3
dyspnea / Early / Incidence not known
hypotension / Rapid / Incidence not known
thrombocytosis / Delayed / Incidence not known
hemolysis / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
wheezing / Rapid / Incidence not known

fatigue / Early / 34.0-34.0
headache / Early / 33.0-33.0
diarrhea / Early / 21.0-21.0
weight gain / Delayed / 8.0-8.0
xerophthalmia / Early / 8.0-8.0
ocular pain / Early / 4.0-4.0
ocular discharge / Delayed / 1.3-1.3
leukocytosis / Delayed / Incidence not known
cough / Delayed / Incidence not known
chills / Rapid / Incidence not known
flushing / Rapid / Incidence not known
dizziness / Early / Incidence not known
myalgia / Early / Incidence not known

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.[63547]

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.[63547]

LUMOXITI

Rx

CD22-directed antibody-drug conjugate toxin
Used for the treatment of relapsed or refractory hairy cell leukemia in adult patients who received at least 2 prior systemic therapies, including treatment with a purine nucleoside analog
Capillary leak syndrome and hemolytic-uremic syndrome have been reported

0.04 mg/kg (actual body weight) IV over 30 minutes on days 1, 3, and 5 repeated every 28 days until disease progression or a maximum of 6 cycles. The dose may be recalculated between cycles if a patient's weight changes by greater than 10% from their initial weight; do not change the dose during a particular cycle. Therapy interruption or discontinuation may be necessary for patients who develop severe toxicity. Stop the infusion if a severe infusion-related reaction occurs. 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 and an oral corticosteroid (e.g., 4 mg dexamethasone) is recommended to decrease the incidence of nausea and vomiting. Administer IV fluids over 2 to 4 hours prior to and after each infusion with 1 L (patients weighing 50 kg or greater) or 0.5 L (patients weighing less than 50 kg) of an isotonic solution (e.g., 5% dextrose injection, 0.45% or 0.9% sodium chloride injection). Oral hydration (e.g., water, milk, or juice) with up to 3 L (twelve 8-oz glasses) in patients weighing 50 kg or greater or up to 2 L (eight 8-oz glasses) in patients weighing less than 50 kg is recommended per 24 hours on days 1 to 8 of each cycle. Consider thromboembolic prophylaxis with low-dose aspirin on days 1 to 8 of each cycle. At a median follow-up of 16.7 months, the objective response rate was 75% and the complete response rate maintained for more than 180 days (primary endpoint) was 30% in patients with relapsed or refractory hairy-cell leukemia who received moxetumomab pasudotox in a multinational, single-arm trial (n = 80). Patients (median age, 60 years; range, 34 to 84 years) had a neutrophil count less than 1 x 109 cells/L, a hemoglobin level less than 10 grams/dL, or symptomatic splenomegaly and had received at least 2 prior systemic therapies (median of 3 prior therapies; range, 2 to 11 therapies) including 2 courses of a purine nucleoside analog or 1 course of rituximab or a BRAF inhibitor following a single course of a purine nucleoside analog.[63548]

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Moxetumomab pasudotox has not been evaluated in patients with moderate or severe hepatic impairment (total bilirubin level greater than 1.5-times the upper limit of normal).[63547]

Baseline Renal Impairment:
Severe renal impairment (creatinine clearance of 29 mL/min or less): Use not recommended.
Treatment-Related toxicity:
Grade 2 or higher elevated serum creatinine (SCr) level (SCr level of greater than 1.5-times baseline or the upper limit of normal (ULN)) in patients with normal SCr at baseline: Interrupt therapy; resume moxetumomab pasudotox when toxicity recovers to grade 1 (SCr level of 1- to 1.5-times baseline or between the ULN and 1.5-times the ULN).Grade 3 or higher elevated SCr level (SCr level of greater than 3-times baseline or the ULN) in patients with grade 1 or 2 elevated SCr level at baseline: Interrupt therapy; resume moxetumomab pasudotox when toxicity recovers to baseline grade or lower.[63547]

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.
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.
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.

LUMOXITI Intravenous Inj Pwd: 1mg

0.04 mg/kg (actual body weight) IV per dose.

0.04 mg/kg (actual body weight) IV per dose.

Safety and efficacy not established.

Safety and efficacy not established.

Safety and efficacy not established.

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.[63547]

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.

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.[63547]

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.

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.[63547]