Moxetumomab Pasudotox, sold under the brand name Lumoxiti, is a type of medication used in the treatment of certain forms of cancer. Specifically, it's used for the treatment of adults with relapsed or refractory hairy cell leukemia (HCL) who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog.

Moxetumomab Pasudotox is a recombinant immunotoxin, meaning it's a type of protein that combines an antibody fragment and a toxin to target and kill specific cells. In the case of Moxetumomab Pasudotox, the antibody portion targets CD22, a protein found on the surface of B cells, including the abnormal B cells found in hairy cell leukemia. The toxin portion then enters these cells and disrupts protein synthesis, causing the cells to die.

This drug is administered intravenously, typically over half an hour every other day for three doses in a 28-day cycle. The exact dosage and length of treatment may vary depending on a patient's specific needs and circumstances.

Moxetumomab Pasudotox (Lumoxiti) is a CD22-directed cytotoxin that consists of the binding fragment of an anti-CD22 antibody fused to a toxin, PE38. It is used in the management of adult patients with hairy cell leukemia.

Moxetumomab Pasudotox (Lumoxiti) Uses:

• Hairy cell leukemia (relapsed or refractory):
  • Therapy of relapsed or refractory hairy cell leukemia (HCL) in adult patients who have received at least two prior systemic therapies, including medication with a purine nucleoside analog.
  • Limitations of use: Moxetumomab pasudotox is not recommended in patients with acute renal impairment (CrCl ≤29 mL/minute).

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Moxetumomab Pasudo to Dose in Adults:

Note: Use your actual body weight before you receive the first dose of the treatment to determine the correct dose. If your weight changes by more than 10% between treatment cycles, a dose adjustment may be made before starting the next cycle. However, do not change the dose during a cycle; wait until the beginning of the next one.

Moxetumomab Pasudotox (Lumoxiti) Dose in the treatment of relapsed or refractory cell leukemia:

Treatment Plan:

• Moxetumomab Pasudotox is given via an IV (in the vein).
• The dose is 0.04 mg for each kilogram you weigh.
• You get this dose on days 1, 3, and 5 of each 28-day treatment cycle.
• This continues for a maximum of 6 cycles, or until the disease gets worse, or if the side effects become too hard to handle.

Additional Treatments:

Hydration:

• Before and after each treatment, you will get 1 L (or 500 mL for people less than 50 kg) of fluid in your IV over 2 to 4 hours.
• Between days 1 and 8 of each 28-day treatment cycle, try to drink up to 3 L (or 2 L for people less than 50 kg) of fluids like water, milk, or juice each day.
• Your doctor will keep an eye on your fluid levels and electrolytes to prevent fluid overload or imbalances.

Pre-medications:

• Before each treatment, you will get medications to prevent side effects.
• These include an antihistamine, an antipyretic (to prevent fever), and a H2-receptor antagonist (to prevent stomach acid production).
• These medications are given 30 to 90 minutes before each treatment.

Post-infusion medications:

• After each treatment, you will get a corticosteroid to decrease nausea and vomiting.
• You might also get antihistamines and antipyretics for up to 24 hours after the treatment.
• Keep drinking plenty of fluids.

Preventing Blood Clots:

• To help prevent blood clots, you may be given low-dose aspirin on days 1 through 8 of each 28-day treatment cycle.

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Moxetumomab Pasudotox dose in Children:

Not indicated.

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Pregnancy Risk Category: N

• The way Moxetumomab Pasudotox works and its side effects in animal studies suggest it might harm both the mother and the baby if used during pregnancy.
• It's important to know if a woman is pregnant before she begins this treatment.
• The company that makes this drug recommends that women who could become pregnant use effective birth control during treatment.
• These women should continue to use birth control for at least 30 days after the last dose of Moxetumomab Pasudotox to prevent possible harm to a baby if a pregnancy occurs.

Use of Moxetumomab during breastfeeding:

• We do not know if Moxetumomab Pasudotox can be passed to a baby through breast milk.
• The company that makes this drug advises against breastfeeding during treatment.
• If a woman is receiving treatment and is breastfeeding, she should discuss with her doctor about either stopping the drug or stopping breastfeeding.
• This decision should weigh the benefits of breastfeeding for the baby against the benefits of the treatment for the mother.

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Moxetumomab Pasudotox (Lumoxiti) Dose in Kidney Disease:

Before Starting Treatment:

• If your kidney function, measured by creatinine clearance (CrCl), is 30 mL/minute or higher, no change in dosage is needed. Research shows that the drug works the same in people with CrCl 30 to 89 mL/minute.
• If your CrCl is 29 mL/minute or lower, it's not recommended to use Moxetumomab Pasudotox because it might be harmful.

During Treatment:

• If your creatinine level rises to more than 1.5 times your baseline (the level before treatment) or the upper limit of normal (ULN):
  • If your creatinine level was normal before treatment, delay (postpone) the next dose.
  • When your creatinine falls to 1 to 1.5 times the baseline or to the ULN to 1.5 times ULN, you can restart treatment.
• If your creatinine level rises to more than 3 times your baseline or the ULN:
  • If your baseline creatinine was slightly above normal (grade 1) or moderately above normal (grade 2), delay the next dose.
  • When your creatinine falls to the same as your baseline or lower, you can restart treatment.

Moxetumomab Pasudotox (Lumoxiti) Dose in Liver disease:

Before and During Treatment:

• For mild liver impairment: If your total bilirubin level is normal or slightly increased, and AST (a liver enzyme) is elevated, there are no changes needed in your dose. Studies show that Moxetumomab Pasudotox works the same in patients with mild liver impairment.
• For moderate to severe liver impairment: If your total bilirubin level is more than 1.5 times the upper limit of normal, the manufacturer does not provide dosage adjustments because it has not been studied. Therefore, it is unclear how the drug might affect you, or how your liver might process the drug.

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Common Side Effects of Moxetumomab Pasudotox (Lumoxiti):

• Cardiovascular:
  • Peripheral Edema
  • Capillary Leak Syndrome
  • Facial Edema
• Central Nervous System:
  • Fatigue
  • Headache
• Endocrine & Metabolic:
  • Hypoalbuminemia
  • Fluid Retention
  • Electrolyte Disorder
  • Hypocalcemia
  • Hypophosphatemia
  • Hyponatremia
  • Hypokalemia
  • Increased Gamma-Glutamyl Transferase
  • Hypomagnesemia
  • Hyperuricemia
• Gastrointestinal:
  • Nausea
  • Constipation
  • Diarrhea
  • Abdominal Distention
• Genitourinary:
  • Nephrotoxicity
• Hematologic & Oncologic:
  • Decreased Hemoglobin
  • Neutropenia
  • Anemia
  • Decreased Platelet Count
• Hepatic:
  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Aminotransferase
  • Increased Serum Bilirubin
  • Increased Serum Alkaline Phosphatase
• Renal:
  • Increased Serum Creatinine
• Miscellaneous:
  • Infusion-Related Reaction
  • Fever

Less Common Side Effects Of Moxetumomab Pasudotox (Lumoxiti):

• Cardiovascular:
  • Edema
  • Pericardial Effusion
• Endocrine & Metabolic:
  • Weight Gain
  • Hypervolemia
• Genitourinary:
  • Proteinuria
• Hematologic & Oncologic:
  • Hemolytic-Uremic Syndrome
  • Febrile Neutropenia
• Hepatic:
  • Ascites
• Local:
  • Localized Edema
• Ophthalmic:
  • Blurred Vision
  • Xerophthalmia
  • Cataract
  • Eye Discomfort
  • Eye Pain
  • Ocular Edema
  • Periorbital Edema
  • Conjunctival Hemorrhage
  • Conjunctivitis
  • Eye Discharge
• Renal:
  • Acute Renal Failure
  • Renal Insufficiency
• Respiratory:
  • Pleural Effusion

• Immunologic:
  • Antibody Development

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Contraindications to Moxetumomab Pasudotox (Lumoxiti):

The manufacturer's labeling does not contain any contraindications.

Warnings and precautions

Capillary leak syndrome: [US-Boxed Warning]

• Moxetumomab Pasudotox can cause a serious condition called Capillary Leak Syndrome (CLS), which can even be life-threatening.
• CLS can lead to low blood pressure, low levels of albumin in the blood, and symptoms related to fluid overload in the body.
• If you're receiving this medication, your weight, blood pressure, and certain blood tests will be monitored regularly.
• If CLS is suspected, treatment may need to be delayed or stopped.
• Most CLS cases happen within the first 8 days of treatment but can occur at any time during the cycle.
• It usually takes around 12 days for the symptoms to go away.
• Signs of CLS include weight gain (increase of 2.5 kg or more than 5% from the first day of the current cycle), low blood pressure, swelling, shortness of breath or cough, fluid in the lungs, and fluid in the body cavities.
• If you notice these signs, seek medical attention immediately because CLS can be deadly if not treated quickly.
• The treatment of CLS may include supportive care like corticosteroids and hospitalization.
• Moxetumomab Pasudotox will be stopped temporarily for mild to moderate CLS until the condition resolves and permanently for severe CLS.

An electrolyte anomaly:

• Moxetumomab Pasudotox can cause problems with the levels of electrolytes in your body.
• More than half of the people treated with this medication experienced these abnormalities, including severe cases.
• The most common problem was low calcium levels.
• These imbalances often happened in the same treatment cycle as Capillary Leak Syndrome (CLS), Hemolytic Uremic Syndrome (HUS), fluid retention, or kidney damage.
• To catch any problems early, your doctor will test your blood for electrolyte levels before each dose and on the 8th day of each treatment cycle.
• Additional tests in the middle of the cycle are also recommended.

Hemolytic Uremic Syndrome: [US Boxed Warn]

• Moxetumomab Pasudotox can cause a serious condition known as Hemolytic Uremic Syndrome (HUS), which can be life-threatening.
• HUS involves the destruction of red blood cells, low platelet count, and kidney failure.
• Most HUS cases occur within the first 9 days of a treatment cycle, but they can happen at any time during the cycle.
• In order to monitor for HUS, your doctor will check your blood for hemoglobin levels, platelet count, and creatinine levels, and also make sure you are well-hydrated.
• If you develop HUS, treatment with Moxetumomab Pasudotox will be stopped.
• Symptoms to watch out for include signs of anemia (like fatigue), sudden onset or worsening of low platelet count, increased creatinine, increased bilirubin and/or LDH, and evidence of red blood cell destruction.
• If HUS is suspected, you will need immediate medical attention, which may include hospitalization, fluid replacement, and monitoring of your blood flow and pressure.
• Delays in treating HUS can lead to life-threatening conditions, like kidney failure that needs dialysis.
• If you have a history of severe HUS, you should avoid Moxetumomab Pasudotox.
• In one study, patients received a low-dose aspirin to prevent blood clots from the first to the eighth day of each 28-day treatment cycle.
• Regular monitoring of blood and chemistry levels will be carried out before each dose and on the eighth day of each treatment cycle.

Infusion reactions

• Infusion reactions are common with Moxetumomab Pasudotox, happening in about half of the people who take it.
• These reactions can happen during any treatment cycle and can be serious.
• Symptoms include chills, fever, dizziness, cough, shortness of breath, feeling hot, flushing, headache, changes in blood pressure, muscle pain, nausea, vomiting, fast heart rate, or wheezing.
• The most common symptoms are nausea, vomiting, fever, chills, and headache.
• To help prevent these reactions, you'll be given antihistamines and fever reducers before each dose.
• If you have a severe reaction during an infusion, the infusion will be stopped and you'll receive medical treatment.
• A corticosteroid will be given about 30 minutes before the infusion is resumed and before the next treatment to help prevent another reaction.

Toxicity in the renal system:

• Kidney damage is a known side effect of Moxetumomab Pasudotox treatment.
• This can range from mild to severe and may include symptoms like acute kidney injury, kidney failure, an increase in creatinine levels in the blood, and protein in the urine.
• Some patients have experienced significant increases in creatinine levels during treatment, including severe increases.
• In a small number of patients, creatinine levels remained high even after the treatment ended.
• People who are over 65, have kidney problems to start with, or develop Hemolytic Uremic Syndrome (HUS) during treatment may have a higher risk of worsening kidney function.
• To catch any kidney problems early, your doctor will check your kidney function before each infusion and as needed during treatment.
• If you have a severe increase in creatinine levels or if your creatinine level increases by two or more grades from the start of treatment, the doctor may delay the doses.

Moxetumomab Pasudotox: Drug Interaction

Risk Factor C (Monitor therapy)
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Risk Factor D (Consider therapy modification)
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely.
Risk Factor X (Avoid combination)
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased

Monitoring parameters:

To ensure safe and effective treatment with Moxetumomab Pasudotox, several important monitoring steps are recommended.

Before Each Dose and on Day 8 of Each Treatment Cycle:

• Obtain a Complete Blood Count (CBC) and check for any abnormalities in the blood.
• Conduct serum chemistry tests to assess the levels of various substances in the blood.

Renal Function Monitoring:

• Check the kidney function before each infusion and as needed throughout the treatment.
• Monitor serum creatinine levels to assess kidney health.

Pregnancy Status Assessment:

• For females who could become pregnant, conduct a pregnancy test before starting the treatment.

Capillary Leak Syndrome (CLS) Monitoring:

• Keep track of body weight and blood pressure before each infusion and as clinically indicated.
• If CLS is suspected, monitor labs, including albumin levels.
• Be aware of signs and symptoms of CLS, such as sudden weight gain (increase of 2.5 kg or ≥5% from the first day of the current cycle), low blood pressure, swelling, shortness of breath or cough, fluid in the lungs, and fluid in body cavities.

Hemolytic Uremic Syndrome (HUS) Monitoring:

• Monitor for signs of HUS, such as increased serum creatinine, elevated bilirubin and/or LDH levels, and evidence of red blood cell destruction based on peripheral blood smear schistocytes.

Other Monitoring:

• Watch for signs and symptoms of infusion reactions, thrombosis (blood clotting), and fluid overload.

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How to administer Moxetumomab Pasudotox (Lumoxiti)?

Here are the steps for taking Moxetumomab Pasudotox:

• It's given by IV (in your vein) and the infusion takes 30 minutes.
• Don't mix this medication with other drugs in the same IV.
• After the medication is given, the IV line will be flushed with normal saline (salt water) at the same rate as the infusion to make sure you get the whole dose.
• You will be given medications 30 to 90 minutes before each dose of Moxetumomab Pasudotox to help prevent side effects. These include an antihistamine, acetaminophen (a pain reliever and fever reducer), and a histamine-2 receptor antagonist (to reduce stomach acid).
• Make sure to drink plenty of fluids to stay well-hydrated.

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Mechanism of action of Moxetumomab Pasudotox (Lumoxiti):

• Moxetumomab Pasudotox is a specially designed drug that targets and kills certain cells in your body.
• It is made up of a part of an antibody that can bind to a protein called CD22, which is found on the surface of B cells, a type of immune cell.
• This antibody part is connected to a piece of a toxin from a bacteria called Pseudomonas.
• When Moxetumomab Pasudotox is given to a patient, the antibody part of the drug binds to the CD22 protein on the B cells.
• This causes the drug to be pulled into the cell, bringing the toxin along with it.
• Inside the cell, the toxin interferes with a protein called elongation factor 2, which is necessary for the cell to make new proteins.
• When this protein is blocked, the cell can't function properly and it dies.
• This is how Moxetumomab Pasudotox can help treat diseases like hairy cell leukemia, which are caused by B cells growing out of control.

Onset of Effect:

• It generally takes about a month to see an improvement in blood counts (hematologic remission).
• After the first three infusions, the number of certain types of blood cells (CD19+ B cells, which are related to the CD22 cells the drug targets) decreased by 89%.

Duration of Effect:

• For patients with minimal remaining disease, the average length of time that the disease stays in complete response is about 6 months.
• The reduction in B cells lasts for at least a month after treatment.

Distribution and Elimination:

• The drug spreads through a volume of about 6.5 liters in the body.
• The half-life of the drug (the time it takes for half of the drug to be eliminated from the body) is about 1.4 hours. This means the drug is removed relatively quickly from the body.

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International Brand Names of Moxetumomab pasudotox:

• Lumoxiti

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Moxetumomab pasudotox Brand Names in Pakistan:

No Brands Available in Pakistan.