MYLOTARG

What Is MYLOTARG and What Is It Used For?

MYLOTARG (gemtuzumab ozogamicin) is an antibody-drug conjugate used to treat CD33-positive acute myeloid leukaemia (AML) in patients aged 15 years and older who have not previously received other treatments. It works by delivering a potent cell-killing agent directly to leukaemic cells that express the CD33 surface protein.

MYLOTARG belongs to a class of cancer medicines known as antibody-drug conjugates (ADCs). It is composed of two key components: a humanised monoclonal antibody that specifically recognises and binds to the CD33 antigen, and a cytotoxic agent called calicheamicin, which is chemically linked to the antibody. CD33 is a transmembrane receptor protein found on the surface of leukaemic blast cells in approximately 85–90% of patients with AML, making it an attractive therapeutic target.

When MYLOTARG is administered intravenously, the antibody component circulates in the bloodstream and seeks out cells expressing CD33 on their surface. Once the antibody binds to CD33, the entire drug-antibody complex is internalised into the cancer cell. Inside the cell, the calicheamicin payload is released from the antibody. Calicheamicin then migrates to the cell nucleus, where it binds to the minor groove of DNA and causes double-strand DNA breaks. These breaks trigger cell cycle arrest and ultimately lead to apoptosis (programmed cell death), effectively destroying the leukaemic cell.

Acute myeloid leukaemia (AML) is a type of blood cancer that originates in the bone marrow. In AML, the bone marrow produces abnormal white blood cells (myeloid blasts) that proliferate uncontrollably, crowding out normal blood cells. This leads to anaemia (low red blood cells), neutropenia (low normal white blood cells causing susceptibility to infections), and thrombocytopenia (low platelets causing bleeding problems). AML is the most common acute leukaemia in adults, with an incidence that increases with age.

MYLOTARG is indicated for the treatment of newly diagnosed, de novo AML in combination with standard daunorubicin and cytarabine chemotherapy, or as monotherapy in patients who are not candidates for intensive chemotherapy. It is approved for patients aged 15 years and older. Importantly, MYLOTARG should not be used to treat acute promyelocytic leukaemia (APL), a distinct subtype of AML that requires specific treatment with all-trans retinoic acid (ATRA) and arsenic trioxide.

What Should You Know Before Receiving MYLOTARG?

Before receiving MYLOTARG, your doctor will assess your liver function, blood counts, and overall health. You should not receive MYLOTARG if you are allergic to gemtuzumab ozogamicin or any of its ingredients. Tell your doctor about all your medical conditions, especially liver problems, previous haematopoietic stem cell transplant, and pregnancy status.

Contraindications

You should not receive MYLOTARG if you have a known allergy (hypersensitivity) to gemtuzumab ozogamicin or to any of the other ingredients of this medicine (listed in the “What Does MYLOTARG Contain?” section). Signs of a severe allergic reaction may include wheezing, difficulty breathing, swelling of the face or throat, hives, and rapid drop in blood pressure.

Warnings and Precautions

Talk to your doctor or nurse before receiving MYLOTARG if you have or have ever had any of the following conditions. Your treatment team needs this information to monitor you appropriately and adjust your care plan:

• Liver problems: MYLOTARG can cause hepatotoxicity, including a potentially life-threatening condition called hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS). In VOD, the small blood vessels in the liver become damaged and blocked by blood clots, which can lead to fluid retention, rapid weight gain, enlarged liver (which may be painful), and ascites (excessive fluid accumulation in the abdomen). The risk of VOD is increased in patients with pre-existing liver disease, in those who receive MYLOTARG before or after haematopoietic stem cell transplantation, and in patients treated with higher cumulative doses.
• Infusion-related reactions: Like other monoclonal antibody-based therapies, MYLOTARG can cause infusion-related reactions, especially during or shortly after the first infusion. Symptoms may include fever, chills, wheezing, difficulty breathing, shortness of breath, cough, hives (urticaria), itching, swelling, chest tightness, and back pain. To reduce this risk, you will receive premedication with a corticosteroid, paracetamol (acetaminophen), and an antihistamine before each infusion.
• Infections: MYLOTARG causes severe and prolonged myelosuppression (reduction in blood cell production), particularly affecting white blood cells. This significantly increases the risk of serious infections, including bacterial, viral, and fungal infections that can be life-threatening. Tell your doctor immediately if you develop fever, chills, or any signs of infection during or after treatment.
• Bleeding: MYLOTARG commonly causes severe thrombocytopenia (low platelet count), which increases the risk of bleeding. You may experience unusual bruising, bleeding gums, nosebleeds, or blood in your stool or urine. Report any bleeding symptoms to your doctor immediately.
• Anaemia: Reduced red blood cell production is common during MYLOTARG treatment. Symptoms include headache, fatigue, dizziness, and pale appearance. You may require red blood cell transfusions.
• Tumour lysis syndrome (TLS): The rapid destruction of leukaemic cells can release large amounts of cellular contents into the bloodstream, causing a potentially life-threatening metabolic disturbance. Symptoms may include dizziness, decreased urine output, confusion, vomiting, nausea, swelling, breathlessness, and irregular heartbeat. Your doctor will monitor your blood chemistry closely and may give you medications to prevent TLS.

Use in Children and Adolescents

MYLOTARG is not recommended for use in children and adolescents under 15 years of age. There is currently limited clinical data on the safety and efficacy of MYLOTARG in this younger population. Clinical trials in paediatric AML are ongoing, and future regulatory approvals may extend the indication to younger patients based on the results of these studies. For patients aged 15 and older, the same dosing and monitoring recommendations apply as for adults.

Pregnancy and Breastfeeding

MYLOTARG can cause serious harm to an unborn baby due to its mechanism of action, which involves causing DNA damage to rapidly dividing cells. You must avoid becoming pregnant during treatment and for at least 7 months after the last dose if you are a woman of childbearing potential. Men should avoid fathering a child during treatment and for at least 4 months after the last dose. Both women and men must use two effective methods of contraception during these periods.

If you or your partner becomes pregnant during treatment, contact your doctor immediately. Before starting MYLOTARG, discuss fertility preservation options with your doctor, as the treatment may affect your ability to have children in the future.

If you are breastfeeding, you must stop breastfeeding during MYLOTARG treatment and for at least one month after the last dose. It is not known whether gemtuzumab ozogamicin passes into breast milk, but given the potential for serious adverse effects in the nursing infant, breastfeeding is contraindicated.

Driving and Operating Machinery

If you feel unusually tired, dizzy, or develop headaches (which are very common side effects of MYLOTARG), you should not drive or operate machinery. These symptoms are particularly common during and shortly after infusion. Wait until the effects have subsided before driving or performing tasks that require alertness.

Other Medicines and MYLOTARG

Tell your doctor or nurse about all medicines you are currently taking, have recently taken, or might take. This includes prescription medicines, over-the-counter medicines, and herbal remedies. While no formal drug interaction studies have been conducted with MYLOTARG, your doctor will consider all your medications when planning your treatment, particularly medicines that may affect liver function or bone marrow.

How Does MYLOTARG Interact with Other Drugs?

No formal clinical drug interaction studies have been conducted with MYLOTARG. However, because gemtuzumab ozogamicin is an antibody-drug conjugate that releases calicheamicin intracellularly, interactions with conventional cytochrome P450 metabolising enzymes are considered unlikely. The primary concern is additive hepatotoxicity and myelosuppression when combined with other agents.

MYLOTARG is typically administered as part of a combination chemotherapy regimen, most commonly with daunorubicin and cytarabine. The pharmacokinetic properties of gemtuzumab ozogamicin suggest that it is unlikely to interact with drugs metabolised through the cytochrome P450 (CYP) enzyme system, because the antibody component is degraded through normal protein catabolism and the calicheamicin derivative acts intracellularly after receptor-mediated endocytosis.

Nevertheless, clinicians should be aware of the following considerations when using MYLOTARG in combination with other agents:

Always inform your treating haematologist about all medications, supplements, and herbal remedies you are taking. Even though formal pharmacokinetic drug interactions are unlikely, the clinical context of severe myelosuppression and hepatotoxicity risk means that careful medication review is essential for patient safety.

What Is the Correct Dosage of MYLOTARG?

MYLOTARG is administered as an intravenous infusion over 2 hours. The dose is calculated based on body surface area (BSA). In combination with chemotherapy for newly diagnosed AML, the recommended dose is 3 mg/m² on days 1, 4, and 7 of induction. Your doctor will determine the exact dosing schedule based on your treatment plan and response.

MYLOTARG is always administered by a healthcare professional in a hospital or specialist clinic setting. It is not a self-administered medication. Before each infusion, you will receive premedication consisting of a corticosteroid (such as dexamethasone), paracetamol (acetaminophen), and an antihistamine (such as diphenhydramine) to help reduce the risk and severity of infusion-related reactions.

Adults and Adolescents (15 Years and Older)

Your doctor may adjust, delay, or discontinue your MYLOTARG treatment based on how you respond and on any side effects you experience. Blood tests will be performed regularly to monitor your blood cell counts, liver function, and overall response to treatment. The decision to continue, modify, or stop treatment will be made by your haematologist based on a careful assessment of the benefits and risks for your individual situation.

Children Under 15 Years

MYLOTARG is not approved for use in children and adolescents under 15 years of age. There is insufficient data on safety and efficacy in this age group. Paediatric patients with AML should be treated according to current paediatric oncology guidelines.

Dose Modifications

Your doctor may need to modify or delay your MYLOTARG doses based on the following considerations:

• Liver function abnormalities: If your liver blood tests become abnormal during treatment, your doctor may delay subsequent doses until values return to acceptable levels.
• Severe myelosuppression: If your blood counts do not recover sufficiently between treatment cycles, the next dose may be delayed.
• Persistent thrombocytopenia: If your platelet count remains critically low, dose adjustment or treatment delay may be necessary.
• Infusion-related reactions: If you experience a severe reaction during infusion, the infusion will be interrupted or discontinued. Your doctor will decide whether further treatment is appropriate.
• Signs of VOD/SOS: If you develop signs of hepatic veno-occlusive disease, treatment will be stopped immediately.

Overdose

There is no specific antidote for MYLOTARG overdose. In the event of an overdose, the patient should be closely monitored for signs and symptoms of adverse reactions, particularly liver toxicity, severe myelosuppression, and infusion-related reactions. Supportive care measures should be initiated as clinically appropriate. Since MYLOTARG is always administered by healthcare professionals in a controlled setting, the risk of accidental overdose is minimised.

What Are the Side Effects of MYLOTARG?

Like all cancer medicines, MYLOTARG can cause side effects, although not everyone gets them. The most common side effects include low blood cell counts (neutropenia, thrombocytopenia, anaemia), infections, fever, nausea, vomiting, abnormal liver blood tests, bleeding, and fatigue. Some side effects can be serious and life-threatening, particularly hepatic veno-occlusive disease (VOD) and severe infections.

MYLOTARG is a potent cancer treatment, and the majority of patients will experience one or more side effects during treatment. Many of these are related to the expected pharmacological action of the drug on rapidly dividing cells, including both leukaemic and normal blood-forming cells in the bone marrow. Your medical team will monitor you closely and provide supportive care as needed.

Your medical team will perform regular blood tests throughout your treatment to monitor for these side effects. If you experience any side effects not listed here, or if any side effect becomes severe, contact your doctor or nurse. Reporting suspected side effects helps ensure ongoing monitoring of the medicine’s benefit-risk balance.

How Should MYLOTARG Be Stored?

MYLOTARG is stored and handled exclusively by healthcare professionals in a hospital or clinic setting. Unopened vials must be stored in a refrigerator (2–8°C), protected from light, and must not be frozen. Once reconstituted or diluted, the solution must be used within specific timeframes.

As a hospital-administered medication, you do not need to store MYLOTARG at home. However, understanding the storage requirements helps you appreciate the careful handling this medicine requires:

• Unopened vials: Store in a refrigerator at 2–8°C. Do not freeze. Keep the vial in the original carton to protect from light.
• After reconstitution: The reconstituted solution in the original vial can be stored for up to 16 hours in a refrigerator (2–8°C) or up to 3 hours at room temperature (below 30°C). Protect from light.
• After dilution: The diluted solution can be stored for up to 18 hours in a refrigerator (2–8°C) and up to 6 hours at room temperature (below 30°C). The maximum time from reconstitution through to completion of administration must not exceed 24 hours.
• Do not freeze the reconstituted or diluted solution.
• Light-sensitive: MYLOTARG must be protected from ultraviolet light during reconstitution, dilution, and administration. The intravenous bag or syringe must be covered with a light-protective shield during infusion.

Do not use this medicine if you notice particles or discolouration before administration. Unused medicine should be disposed of according to local requirements for cytotoxic waste.

What Does MYLOTARG Contain?

Each MYLOTARG vial contains 5 mg of the active ingredient gemtuzumab ozogamicin as a white to off-white powder (lyophilisate). After reconstitution with water for injection, the concentrated solution contains 1 mg/mL of gemtuzumab ozogamicin.

Active Ingredient

The active substance is gemtuzumab ozogamicin, an antibody-drug conjugate consisting of a humanised anti-CD33 IgG4 monoclonal antibody covalently linked to the cytotoxic agent N-acetyl-gamma-calicheamicin. Each vial contains 5 mg of gemtuzumab ozogamicin. When reconstituted according to the instructions, the solution contains 1 mg/mL. The extractable volume from each vial is approximately 4.5 mL (4.5 mg), as there is no overfill.

Inactive Ingredients (Excipients)

The other ingredients are:

• Dextran 40 – a branched polysaccharide used as a stabiliser
• Sucrose – a sugar used as a lyoprotectant during freeze-drying
• Sodium chloride – for tonicity adjustment
• Sodium dihydrogen phosphate monohydrate – buffer component
• Disodium hydrogen phosphate (anhydrous) – buffer component

Sodium Content

This medicine contains less than 1 mmol (23 mg) sodium per dose, meaning it is essentially “sodium-free.” This is relevant for patients on a sodium-restricted diet or receiving multiple intravenous medications with sodium content.

Packaging and Appearance

MYLOTARG is supplied as a white to off-white lyophilised cake or powder in a single-use amber glass vial with a rubber stopper and aluminium seal with a flip-off cap. Each carton contains one vial. The reconstituted solution should be a clear to slightly opalescent liquid, and may contain small white to off-white, opaque to translucent, amorphous to fibre-like particles.

How Does MYLOTARG Work in the Body?

MYLOTARG works by targeting the CD33 protein found on the surface of most AML leukaemic cells. Once the antibody binds to CD33 and the complex is internalised into the cell, the cytotoxic calicheamicin payload is released, causing irreversible DNA damage that kills the cancer cell through apoptosis.

The mechanism of action of MYLOTARG can be understood as a three-step process of targeting, internalisation, and cell killing:

Step 1 – Targeting: The humanised IgG4 monoclonal antibody component of MYLOTARG specifically recognises and binds to the CD33 antigen (also known as Siglec-3), a sialic acid-binding immunoglobulin-like lectin expressed on the surface of myeloid lineage cells. CD33 is present on the surface of leukaemic blasts in approximately 85–90% of AML patients, making it a highly selective target. Importantly, CD33 is not expressed on pluripotent haematopoietic stem cells, which means that normal blood cell regeneration can occur after treatment.

Step 2 – Internalisation: After the antibody binds to CD33, the drug-receptor complex is rapidly internalised into the cell via receptor-mediated endocytosis. The complex enters the endosomal-lysosomal pathway, where the acidic pH environment triggers the cleavage of the acid-labile linker connecting the antibody to the calicheamicin payload.

Step 3 – Cell killing: The released calicheamicin derivative migrates to the cell nucleus and binds to the minor groove of DNA. This binding causes double-strand DNA breaks through a free radical mechanism. The extensive DNA damage overwhelms the cell’s repair mechanisms, triggering cell cycle arrest and ultimately apoptosis (programmed cell death). This mechanism is effective against both dividing and non-dividing leukaemic cells.

Pharmacokinetic Profile

After intravenous infusion, gemtuzumab ozogamicin is distributed primarily to the blood compartment. The half-life of the antibody component is approximately 62–72 hours after the first dose, increasing to approximately 90–100 hours after the second dose. This increase in half-life is thought to reflect decreased CD33 antigen load as leukaemic cells are eliminated during treatment.

The total unconjugated calicheamicin (the active cytotoxic component after intracellular release) has a short half-life, reflecting its rapid intracellular action and metabolism. Calicheamicin is primarily metabolised through non-enzymatic reduction of its disulphide bonds and demethylation. Because the drug acts intracellularly after receptor-mediated endocytosis, systemic drug interactions via the cytochrome P450 system are considered unlikely.

Population pharmacokinetic analyses suggest that body surface area, baseline CD33 expression levels, and leukaemic blast count may influence the pharmacokinetics of MYLOTARG. However, dose adjustments based on these factors are not routinely recommended, as the approved dosing regimen has been optimised through clinical trials.

Frequently Asked Questions About MYLOTARG