Gemtuzumab ozogamicin, commonly known by its trade name Mylotarg, is a type of drug known as an antibody-drug conjugate (ADC). It is designed to specifically target cancer cells in the treatment of acute myeloid leukemia (AML).

Gemtuzumab Ozogamicin (Mylotarg) is an antibody-drug conjugate that is indicated for the treatment of CD-33 +ve acute myeloid leukemia and is used as an off-label treatment in patients with acute promyelocytic leukemia.

Gemtuzumab ozogamicin Uses:

• Acute myeloid leukemia (newly diagnosed):
  • It is indicated in the treatment of newly diagnosed CD33-positive acute myeloid leukemia (AML) in adults.
• Acute myeloid leukemia (relapsed/refractory):
  • it is indicated in the treatment of relapsed/refractory CD33-positive acute myeloid leukemia (AML) in adults and pediatric patients ≥2 years.
• Off Label Use of Gemtuzumab ozogamicin in Adults:
  • Acute promyelocytic leukemia

Gemtuzumab Ozogamicin (Mylotarg) dose in Adults

Note:

Before you get the infusion:

• Take a 650 mg acetaminophen pill (like Tylenol).
• Take a 50 mg diphenhydramine pill (like Benadryl) or get it through an IV.
• These two should be taken about 1 hour before the infusion.
• Also, take methylprednisolone (a type of steroid) or something similar.
• This should be taken either by mouth or through an IV about 30 minutes before the infusion.
• The dose should be 1 mg for every kg of your body weight.

After the infusion starts:

• If you need, you can take more acetaminophen and diphenhydramine every 4 hours.
• If during or within 4 hours after the infusion you experience symptoms like fever, chills, low blood pressure, or difficulty breathing, you should take another dose of methylprednisolone or its equivalent.

Dose in the treatment of newly diagnosed acute myeloid leukemia: IV:

When used with other drugs (combination therapy):

• Treatment Plan: 1 induction cycle + 2 consolidation cycles (alongside other drugs).
  • Induction (Start): 3 mg for every meter square of your body's surface area, but not more than 4.5 mg per dose. This is given on days 1, 4, and 7, along with daunorubicin and cytarabine. If you need a second starting cycle, skip gemtuzumab ozogamicin.
  • Consolidation (Follow-up): You get 2 cycles. For each cycle, take 3 mg/m^2 (but no more than 4.5 mg each time) on day 1. This is also given with daunorubicin and cytarabine.

When used alone (single-agent):

• Treatment Plan: 1 induction cycle + up to 8 continuation cycles.
  • Induction (Start): 6 mg for every meter square of your body's surface area on day 1. Then, 3 mg/m^2 on day 8.
  • Continuation (Follow-up): 2 mg/m^2 on the first day of every 4-week period. You can do this for up to 8 times.

Off-label use (Not the standard but sometimes used):

• For adults under 60 with good genetic indicators:
  • Take 3 mg/m^2 on the first day of the 1st and 3rd courses. This is used alongside other chemotherapy drugs.

Gemtuzumab Ozogamicin (Mylotarg) dose in the treatment of relapsed/ refractory Acute myeloid leukemia:

• Dose: 3 mg for every meter square of your body's surface area, but not more than 4.5 mg per dose.
• Schedule: You take this dose on days 1, 4, and 7.
• Type of Therapy: Gemtuzumab ozogamicin is used as a single treatment course.

Gemtuzumab Ozogamicin (Mylotarg) Dose in Acute promyelocytic leukemia (off-label): IV:

When used alone (single-agent therapy) for relapsed disease:

• Dose: 6 mg for every meter square of your body's surface area.
• Schedule: This dose is given on days 1 and 15. If after two doses a patient tests PCR negative, a third dose is given.

When used with other drugs (combination therapy) for high-risk, newly diagnosed patients:

• Induction (Start): 9 mg/m^2 given as a one-time dose on day 1. This is used along with arsenic trioxide and tretinoin.

Post-remission treatment (used if other drugs were stopped due to side effects):

• Dose: 9 mg/m^2
• Schedule: This dose is given once every 4 to 5 weeks and continues until 28 weeks after the patient has achieved complete remission.

Gemtuzumab Ozogamicin (Mylotarg) dose in Childrens

Note:

Before your infusion:

• 1 hour before:
  • Take acetaminophen (like Tylenol). The dose is based on your weight: 15 mg for each kg you weigh, but don't take more than 650 mg in total.
  • Also, take diphenhydramine (like Benadryl). It's 1 mg for each kg you weigh. You can take it as a pill or get it through an IV, but don't take or receive more than 50 mg in total.
• 30 minutes before:
  • Take methylprednisolone (a type of steroid) or have it through an IV. It's 1 mg for each kg you weigh.

After the infusion starts:

• If you need, you can take more acetaminophen and diphenhydramine every 4 hours.
• If you feel any bad reactions (like fever, coldness, low blood pressure, or trouble breathing) during the infusion or within 4 hours after, take another dose of methylprednisolone or another similar steroid.

Gemtuzumab Ozogamicin (Mylotarg) Dose in the treatment of CD33+ Acute myeloid leukemia, newly diagnosed (de novo) or refractory/relapse:

Limited data available in de novo diagnosis or as combination therapy:

For gemtuzumab ozogamicin in treating Acute Myeloid Leukemia (AML) with CD33+ in children and adolescents:

Monotherapy (using this drug alone):

• Age: Kids 2 years and older, and teenagers.
• Dose: 3 mg per square meter of body surface area (BSA) per dose. The maximum you can take is 4.5 mg per dose.
• Schedule: Given on days 1, 4, and 7. If the AML has returned or didn't respond to initial treatment, you only take one course.

Combination therapy (using this drug with others):

• For starting the treatment (Induction):
  • For those with BSA less than 0.6 square meters:
    • 0.1 mg per kg of body weight given once on day 6.
    • This is given with other drugs: cytarabine, daunorubicin, and etoposide.
  • For those with BSA of 0.6 square meters or more:
    • 3 mg per square meter given once on day 6.
    • Also combined with the drugs: cytarabine, daunorubicin, and etoposide.
• For the second intensive treatment (Intensification course 2):
  • For those with BSA less than 0.6 square meters:
    • 0.1 mg per kg of body weight given once on day 7.
    • This is given with cytarabine and mitoxantrone.
  • For those with BSA of 0.6 square meters or more:
    • 3 mg per square meter given once on day 7.
    • Also combined with the drugs: cytarabine and mitoxantrone.

Gemtuzumab Ozogamicin (Mylotarg) Dosing adjustment for toxicity:

For Kids (2 years or older) & Teens:

• Infusion-related reactions:
  • If the patient starts having a reaction during the infusion, stop the infusion.
  • Give treatments like acetaminophen, diphenhydramine, and/or methylprednisolone if needed.
  • If the symptoms go away, consider restarting the infusion but at a slower rate (half the original speed).
  • If the reaction comes back, repeat the above steps.
  • If the reaction is very bad or life-threatening, stop gemtuzumab ozogamicin forever.
• Severe bleeding:
  • Might need to delay the treatment or even stop it permanently.
• Other serious bad reactions:
  • Delay giving gemtuzumab ozogamicin until the bad reaction becomes mild.
  • If you need to delay more than 2 days between infusions, skip the planned dose.
• Blood-related issues (when given with other cancer drugs):
  • The adjustments are based on what doctors have seen in adults. If a specific guide for kids is available, use that.

For Adults:

• Low platelet count (thrombocytopenia):
  • If the platelet count doesn't reach 100,000/mm or more within 14 days when you're supposed to start the next round (after recovering from the previous one), don't use gemtuzumab ozogamicin for that round.
• Low white blood cell count (neutropenia):
  • If the neutrophil count doesn't go above 500/mm within the same 14-day window, again, don't use gemtuzumab ozogamicin for that round.

Gemtuzumab Ozogamicin Pregnancy Category: D

For Women:

• If you're pregnant or planning to become pregnant, don't use gemtuzumab ozogamicin.
• If you're a woman of childbearing age and you're getting this treatment, make sure you're not pregnant.
• While you're getting treated and for at least 6 months after the last dose, use good birth control to avoid getting pregnant.

For Men:

• If you're a man getting this treatment and you have a partner who could get pregnant, be careful.
• Use effective contraception during treatment and for at least 3 months after your last dose.
• This treatment might affect your ability to have kids.

Gemtuzumab ozogamicin is used during breastfeeding

• It's unclear if this drug gets into breast milk.
• Because of potential risks to a baby who is breastfed, the drug maker recommends:
  • Not breastfeeding while on this treatment.
  • Continuing to avoid breastfeeding for at least 1 month after the last dose.

Gemtuzumab Ozogamicin (Mylotarg) Dose in Kidney disease:

• If your kidneys filter at a rate of 30 to 89 mL/minute (CrCl 30 to 89 mL/minute):
  • The manufacturer doesn't give any specific dose changes.
  • Research suggests that, in this range, the way the body processes the drug doesn't change in a way that's concerning.
• If your kidneys filter at a rate of 15 to 29 mL/minute (CrCl 15 to 29 mL/minute):
  • Again, the manufacturer doesn't provide any specific dose changes.
  • This is because they haven't studied the drug in people with this level of kidney function.

Gemtuzumab Ozogamicin (Mylotarg) Dose in Liver disease:

For People with Pre-existing Liver Issues:

• Mild Liver Issue:
  • The manufacturer doesn't suggest any dose changes.
  • Studies show that mild liver problems don't notably change how the body handles the drug.
• Moderate and Severe Liver Issue:
  • The manufacturer doesn't give any specific dose changes.
  • This is because the drug hasn't been studied in people with these levels of liver impairment.

If Liver Issues Develop During Treatment:

• High Bilirubin or Liver Enzymes:
  • If bilirubin (a liver health marker) is more than double the upper limit OR if AST/ALT (liver enzymes) are more than 2.5 times the upper limit:
    1. Wait to give gemtuzumab ozogamicin until these numbers drop to safer levels.
    2. If you have to wait more than 2 days between planned doses, skip the upcoming dose.
• Veno-occlusive disease (VOD, a specific liver issue):
  • Stop using gemtuzumab ozogamicin.

Common Side Effects of Gemtuzumab Ozogamicin (Mylotarg):

• Cardiovascular:
  • Cardiotoxicity
• Central Nervous System:
  • Fatigue
  • Headache
• Dermatologic:
  • Skin Rash
• Hematologic & Oncologic:
  • Hemorrhage
  • Febrile Neutropenia
• Hepatic:
  • Hepatotoxicity
  • Increased Serum AST
  • Increased Serum ALT
• Infection:
  • Infection
• Miscellaneous:
  • Fever

Less Common Side Effects of Gemtuzumab Ozogamicin (Mylotarg):

• Genitourinary:
  • Nephrotoxicity
• Hepatic:
  • Hyperbilirubinemia

Contraindications to Gemtuzumab Ozogamicin (Mylotarg):

• If someone is allergic to gemtuzumab ozogamicin or any part of the drug, they shouldn't take it.

Warnings and precautions

Suppression of bone marrow

• This drug can weaken the bone marrow, which makes blood cells. Because of this, there's a risk of a long-lasting low platelet count (lasting more than 42 days after a dose).
• Before each dose of the drug, and often after finishing the treatment, it's important to check blood counts.
• If there are any issues with blood counts, the patient should get the usual treatments and support they'd get for that issue.

Hemorrhage

• This drug can cause serious or even deadly bleeding due to a long-lasting low platelet count.
• In one study, over 90% of patients had a reduced platelet count, and 20% had severe reductions.
• There were deadly bleeding events in some patients, including bleeding in the brain.
• Before each dose and until the blood counts return to normal, it's important to check the platelet count. Also, watch out for signs of bleeding.
• If there's serious bleeding, other related problems, or the platelet count stays low, treatment might need to be paused or even stopped permanently. Supportive care should be given as needed.

Hepatotoxicity: [US Boxed Warning]

• This drug can cause serious liver problems, including a severe and sometimes deadly condition called hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).
• After taking gemtuzumab ozogamicin, it's important to frequently watch for signs of VOD.
• In a study, VOD typically appeared around 9 days after taking the drug, but it could show up anywhere from 2 to 298 days later. Some cases even occurred over a month after the last dose.
• The risk of VOD might be higher in adults taking larger doses of gemtuzumab ozogamicin alone, people with moderate to severe liver issues before treatment, those getting a hematopoietic stem cell transplant (HSCT) after the drug, and people who get the transplant after this treatment.
• Keep an eye out for symptoms like rapid weight gain, abdominal swelling, liver enlargement (which could hurt), and increased bilirubin and liver enzyme levels.
• Before each dose, check ALT, AST, total bilirubin, and alkaline phosphatase levels. If there are liver function issues during treatment, test more often and pay attention to symptoms.
• If you're getting a transplant after this treatment, it might be good to wait for about 2 months after the last dose.
• If liver problems happen, the dose might need to be paused or the treatment stopped.

Hypersensitivity and Infusion Reaction:

• This drug can cause serious liver problems, including a severe and sometimes deadly condition called hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).
• After taking gemtuzumab ozogamicin, it's important to frequently watch for signs of VOD.
• In a study, VOD typically appeared around 9 days after taking the drug, but it could show up anywhere from 2 to 298 days later. Some cases even occurred over a month after the last dose.
• The risk of VOD might be higher in adults taking larger doses of gemtuzumab ozogamicin alone, people with moderate to severe liver issues before treatment, those getting a hematopoietic stem cell transplant (HSCT) after the drug, and people who get the transplant after this treatment.
• Keep an eye out for symptoms like rapid weight gain, abdominal swelling, liver enlargement (which could hurt), and increased bilirubin and liver enzyme levels.
• Before each dose, check ALT, AST, total bilirubin, and alkaline phosphatase levels. If there are liver function issues during treatment, test more often and pay attention to symptoms.
• If you're getting a transplant after this treatment, it might be good to wait for about 2 months after the last dose.
• If liver problems happen, the dose might need to be paused or the treatment stopped.

Extendation of the QT interval:

• Severe allergic reactions (like anaphylaxis) and other reactions during the infusion can happen within 24 hours of getting the drug. These can be very dangerous or even deadly.
• Signs of these reactions can include fever, chills, low blood pressure, fast heartbeat, low oxygen levels, or breathing problems.
• To help prevent these reactions, take acetaminophen, diphenhydramine, and methylprednisolone before each dose.
• While getting the drug, your vital signs (like heartbeat and blood pressure) should be checked often.
• If you start having a reaction, especially trouble breathing, wheezing, or low blood pressure, the infusion should be stopped right away.
• After the infusion, you should be watched for at least 1 hour or until any symptoms go away completely.
• If you have a severe allergic reaction, especially with major breathing problems or significant low blood pressure, you should never take gemtuzumab ozogamicin again.

Tumor lysis syndrome

• Gemtuzumab ozogamicin is related to other drugs that have been known to make the QT interval longer. The QT interval is a measurement on an ECG that reflects the time it takes for the heart muscle to contract and then recover.
• If the QT interval is too long, it can cause heart rhythm problems.
• Before starting gemtuzumab ozogamicin, get an ECG to check the QT interval and also check the levels of electrolytes (like potassium and calcium) in the blood.
• Pay special attention and possibly get more ECGs in people:
  • With a history or risk of longer QT intervals.
  • Taking other medications known to affect the QT interval.
  • With imbalances in their electrolytes.

Acute myeloid Leukemia with adverse-risk Cytogenetics

• When gemtuzumab ozogamicin was added to the usual chemotherapy for AML patients with certain high-risk genetic features, it didn't seem to help them stay free of the disease any longer.
• So, if someone has these high-risk genetic features, doctors need to weigh the pros and cons before deciding to combine gemtuzumab ozogamicin with standard chemotherapy.

Gemtuzumab Ozogamicin: 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.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Tertomotide	Immunosuppressants may diminish the therapeutic effect of Tertomotide.
Trastuzumab	May enhance the neutropenic effect of Immunosuppressants.
Risk Factor D (Consider therapy modification)
Baricitinib	Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted.
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Fingolimod	Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
Leflunomide	Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy.
Tofacitinib	Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Risk Factor X (Avoid combination)
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Belimumab	Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab.
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Natalizumab	Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
Pimecrolimus	May enhance the adverse/toxic effect of Immunosuppressants.
Tacrolimus (Topical)	May enhance the adverse/toxic effect of Immunosuppressants.
Vaccines (Live)	Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants.

Monitoring parameters:

Liver & Blood Health:

• Liver Function:
  • Check ALT, AST, total bilirubin, and alkaline phosphatase before each dose.
  • Check more often if there's a risk of VOD or in patients having a stem cell transplant (HSCT).
• Blood Counts:
  • Test before each dose.
  • Test at least 3 times a week until recovery from any side effects.
• Chemicals in the Blood:
  • Check serum chemistry at least 3 times a week until recovery from side effects.
• Electrolytes:
  • Monitor levels regularly.

Heart & Pregnancy:

• Pregnancy:
  • Confirm pregnancy status in women who can become pregnant before starting treatment.
• Heart Health:
  • Get an ECG before starting treatment.
  • Check ECG more if there's a history or risk of longer QT intervals, or in those taking QT-prolonging meds or with electrolyte imbalances.

During and After Infusion:

• Infusion Reactions:
  • Watch during and for at least 1 hour after infusion for any reactions.
• VOD Symptoms:
  • Look out for rapid weight gain, liver enlargement, and fluid buildup (ascites).
• Bleeding:
  • Watch for signs like unusual bruising or blood in urine or stool.
• Tumor Lysis Syndrome:
  • Monitor for sudden changes in kidney function, irregular heartbeat, or seizures.

How to administer Gemtuzumab Ozogamicin (Mylotarg)?

Infusion Process:

• Use a 0.2-micron polyethersulfone (PES) in-line filter.
• Give the medicine over 2 hours.
• Make sure the IV bag is shielded from light. Use a cover that blocks out light. (The tube delivering the medicine doesn't need protection from light.)
• Don't give this medicine quickly as an IV push or bolus.

Before the Infusion:

• Give the patient pre-medications: acetaminophen, diphenhydramine, and methylprednisolone. (Refer to the Dosing section for details.)

Monitoring:

• Watch the patient for any reactions during the infusion and for at least 1 hour after it's finished.

Mixing:

• Don't mix this medicine with any other medications or infuse them together.

Mechanism of action of Gemtuzumab Ozogamicin (Mylotarg):

What It Is:

• It's a kind of medicine made by combining parts of a human antibody (gemtuzumab) with a powerful chemical (calicheamicin).
• This mix is called a monoclonal antibody-drug conjugate.

Targets AML Cells:

• It goes after a marker called CD33, which is found on leukemia cells in many AML patients.
• Over 80% of AML patients have CD33 on their leukemic cells.

How It Acts:

• The medicine sticks to CD33, which makes the whole antibody-CD33 combo get inside the leukemia cells.
• Once inside, the calicheamicin part gets released. This is the strong chemical.
• Calicheamicin binds to the DNA in the leukemia cell, causing breaks in the DNA.
• This messes up the cell's cycle and forces it to stop growing. Eventually, the cell dies (apoptosis).

In short, gemtuzumab ozogamicin targets leukemia cells by attaching to CD33, gets inside the cells, and releases a potent chemical that damages their DNA, stopping their growth and causing them to die.

Distribution:

• The antibody part spreads throughout a space of about 21.4 liters in the body.

Protein Binding:

• For the calicheamicin part: About 97% of it sticks to proteins in the blood.

Metabolism:

• The calicheamicin part gets broken down a lot. This mainly happens by a non-enzyme process that changes its structure.

How Long It Lasts in the Body:

• Based on a 9 mg/m^2 dose:
  • The antibody part lasts:
    • About 62 hours after the first dose.
    • About 90 hours after the second dose.

Removal from the Body:

• Based on a 9 mg/m^2 dose:
  • The body gets rid of the antibody part at a rate of:
    • 0.35 liters per hour after the first dose.
    • 0.15 liters per hour after the second dose.

International Brand Names of Gemtuzumab ozogamicin:

• Mylotarg

Gemtuzumab ozogamicin Brand Names in Pakistan:

Not available.