I. [Basic Drug Information]

Generic Name: Gemtuzumab

English Name: Gemtuzumab ozogamicin for Injection

Brand Name: Mylotarg

Dosage Form: Sterile lyophilized powder for injection (requires reconstitution before use)

Specification: 5 mg/vial (calculated as gemtuzumab)

ATC Code: L01FX17 (Antibody-Drug Conjugate, ADC)

Molecular Structure: Humanized IgG4 monoclonal antibody (targeting CD33)

Conjugated Cytotoxin: Calicheamicin

Manufacturer: Pfizer Inc (Pfizer Turkey)

II. [Mechanism of Action]

Mylotarg is an Antibody-Drug Conjugate (ADC):

1. Targeted Recognition: The antibody component specifically binds to the CD33 antigen on the surface of leukemia cells (expressed in >90% of AML cases).

2. Cellular Internalization: The complex is endocytosed into the cell.

3. Toxin Release: Calicheamicin (a potent inducer of DNA double-strand breaks) is released within the lysosomes.

4. Apoptosis Induction: Causes irreversible DNA damage → leading to leukemia cell death.

Advantages:

Precisely targets CD33⁺ cells, minimizing widespread damage to normal hematopoietic stem cells.

When used in combination with chemotherapy, it can increase remission rates and prolong survival.

III. [Indications]

Indications Approved by China's NMPA (2021):

1. Newly diagnosed CD33-positive Acute Myeloid Leukemia (AML) in adults.

In combination with Daunorubicin + Cytarabine (DA regimen).

Indicated for patients aged ≥55 years who are not candidates for intensive chemotherapy (e.g., due to multiple comorbidities or poor performance status).

2. Relapsed or Refractory (R/R) AML.

Monotherapy (regardless of age).

Additional Indications Approved by FDA/EMA:

Newly diagnosed AML (in children aged >1 month and adults), regardless of whether they are candidates for intensive chemotherapy.

R/R AML (aged ≥1 month).

CD33 expression testing is mandatory! The drug is ineffective in patients with negative results. IV. [Usage and Dosage] (Key: Low-dose, fractionated administration!)

Since 2017, the global standard has adopted a "fractionated low-dose" regimen (replacing the earlier high-dose single-administration regimen, thereby significantly reducing toxicity).

▶ Newly Diagnosed AML (Combination Chemotherapy):

Dosage: 3 mg/m² (Actual dose calculated based on Body Surface Area [BSA], but not to exceed 4.5 mg per dose).

Administration Days: Days 1, 4, and 7 (Total: 3 doses).

Combination Regimen:

Daunorubicin 60 mg/m² IV on Days 1–3

Cytarabine 100 mg/m² CIV (Continuous IV Infusion) on Days 1–7

▶ Relapsed/Refractory AML (Monotherapy):

Dosage: 3 mg/m²

Administration Days: Days 1, 4, and 7 (One cycle consists of 28 days).

Maximum Single Dose: 4.5 mg

Example: For a patient with a BSA of 1.7 m² → Single dose = 3 × 1.7 = 5.1 mg → However, the upper limit is 4.5 mg; therefore, 4.5 mg is administered.

V. [Administration Method]

1. Reconstitution:

Dissolve 5 mg of lyophilized powder in 1 mL of sterile water for injection → Yields a 5 mg/mL solution.

2. Dilution:

Transfer the solution into a 50 mL bag of 0.9% Sodium Chloride Injection.

Do *not* use dextrose (glucose) solutions (may cause aggregation).

3. Infusion:

Administer via intravenous infusion over ≥2 hours.

Use a 0.22 μm low-protein-binding filter (to prevent particulate matter).

4. Pre-medication (Mandatory!):

Acetaminophen 650 mg PO

Diphenhydramine 50 mg IV/PO

Hydrocortisone 100 mg IV (To prevent infusion-related reactions).

VI. [Adverse Reactions]

▶ Most Common (≥20%):

Infection (including febrile neutropenia)

Nausea, vomiting

Hemorrhage (due to thrombocytopenia)

Abnormal liver function (elevated ALT/AST)

Rash

▶ Serious Adverse Reactions (Boxed Warning):

Adverse Reactions Incidence | Management

-------- | ------

Hepatotoxicity (including VOD/SOS) | 10–15% (↑ with combination chemotherapy) | Monitor bilirubin, transaminases; Contraindicated prior to HSCT

Myelosuppression | Neutropenia >90%

| Thrombocytopenia >80% | Supportive care (G-CSF, blood transfusions)

Infusion-related reactions | ~20% (fever, chills, hypotension) | Premedication + slow infusion rate

Hemorrhage | 20–30% (especially with platelets <50×10⁹/L) | Avoid traumatic procedures

Sinusoidal Obstruction Syndrome (SOS/VOD):

Manifestations: Rapid weight gain, ascites, jaundice, hepatomegaly

Extremely high risk post-HSCT → Mylotarg should be discontinued at least 2 months prior to transplantation

VII. [Contraindications]

Hypersensitivity to gemtuzumab or calicheamicin

Active severe liver disease (Child-Pugh B/C)

Patients scheduled to undergo hematopoietic stem cell transplantation (HSCT)—timing requires careful assessment

Pregnancy (Category D: Teratogenic, fetal death)

VIII. [Drug Interactions]

Hepatotoxic drugs (e.g., acetaminophen overdose, amphotericin B): ↑ Risk of liver injury

Other myelosuppressive agents (e.g., cytarabine, daunorubicin): Synergistic suppression; requires close monitoring of blood counts

P-gp inhibitors (e.g., verapamil): May ↑ calicheamicin concentrations (theoretical risk)

IX. [Use in Specific Populations]

Population | Recommendation

------ | ------

Pregnant Women | Contraindicated! May cause fetal harm; women of childbearing potential must use effective contraception during treatment and for 7 months after discontinuing the drug.

Lactation: Discontinue breastfeeding (excreted into breast milk).

Pediatric Patients (≥1 month of age): Approved by FDA/EMA for newly diagnosed and relapsed/refractory (R/R) AML; pediatric indications have not yet been approved in China.

Geriatric Patients (≥60 years of age): Higher susceptibility to hepatotoxicity and infections; no initial dose adjustment required, but enhanced monitoring is recommended.

Hepatic Impairment: Bilirubin >2× ULN: Avoid use.

X. Pharmacokinetics

Parameter | Characteristics

------ | ------

Half-life | Approx. 48–96 hours (antibody component)

Volume of Distribution | 5–8 L (confined to the intravascular space)

Metabolism | Antibody: Proteolytic degradation; Calicheamicin: Hepatic CYP450 (minor pathway)

Excretion | Urine (<10%), Feces

Calicheamicin Potency: Extremely potent; a single molecule can kill a single cell.

XI. Storage Conditions

Unopened:

Store refrigerated at 2°C to 8°C, protected from light (do not freeze).

Store in original packaging; protect from moisture.

Shelf Life: 24 months.

After Reconstitution:

Room Temperature (≤25°C): Use within 4 hours.

Refrigerated (2–8°C): Up to 24 hours (protected from light).

Do not use if the reconstituted solution appears cloudy, discolored, or contains particulate matter!

XII. Important Clinical Warnings

1. Must be administered in a specialized hematology center equipped with emergency resuscitation facilities!

2. Pre-administration checks (prior to each dose):

Complete blood count (CBC), Liver function tests (ALT/AST, Bilirubin), Coagulation profile.

3. Patients undergoing HSCT:

Mylotarg is significantly associated with an increased risk of SOS/VOD (Sinusoidal Obstruction Syndrome/Veno-occlusive Disease).

It is recommended to discontinue the drug at least 2 months prior to transplantation.

4. Patient Education:

Seek immediate medical attention if symptoms such as right upper quadrant abdominal pain, jaundice, or rapid weight gain occur.

Avoid the use of NSAIDs (increases the risk of bleeding).

Summary

Mylotarg® (gemtuzumab ozogamicin) is the world's first approved Antibody-Drug Conjugate (ADC), utilizing a "biological missile" mechanism to precisely target CD33⁺ leukemia cells. The optimized fractionated low-dose regimen (3 mg/m² × 3) has significantly improved safety, establishing it as a vital treatment option for elderly or "unfit" patients with AML.

"Targeted Delivery, Precise Killing"—while controlling toxicity, it strives to achieve deeper remission and prolonged survival for patients with AML.

Product Specifications

Product Name: CD33 Gemtuzumab 5 mg/vial (Mylotarg; Gemtuzumab Ozogamicin for Injection)

Generic Name: Gemtuzumab

Composition: Gemtuzumab

Dosage Form: Sterile lyophilized powder for injection (requires reconstitution prior to use)

Specification: 5 mg/vial

Manufacturer: Pfizer Inc (Pfizer Turkey)

Indications: Approved indications by China's NMPA (2021):

1. Newly diagnosed CD33-positive Acute Myeloid Leukemia (AML) in adults

In combination with Daunorubicin + Cytarabine (DA regimen)

Indicated for patients aged ≥55 years who are not candidates for intensive chemotherapy (e.g., due to multiple comorbidities or poor performance status).

2. Relapsed or Refractory (R/R) AML

As monotherapy (regardless of age).

Additional Indications (FDA/EMA):

Newly diagnosed AML (in children ≥1 month of age and adults), regardless of eligibility for intensive chemotherapy.

R/R AML (in patients ≥1 month of age).

CD33 expression testing is mandatory! The treatment is ineffective in patients with negative results. Dosage and Administration: ▶ Newly Diagnosed AML (in combination with chemotherapy):

Dose: 3 mg/m² (Actual dose calculated based on Body Surface Area, but not to exceed 4.5 mg per dose)

Administration Days: Days 1, 4, and 7 (total of 3 doses)

Combination Regimen:

Daunorubicin 60 mg/m² IV on Days 1–3

Cytarabine 100 mg/m² CIV on Days 1–7

▶ Relapsed/Refractory AML (as monotherapy):

Dose: 3 mg/m²

Administration Days: Days 1, 4, and 7 (one cycle consists of 28 days)

Maximum Single Dose: 4.5 mg

Example: For a patient with a Body Surface Area of 1.7 m² → Single dose = 3 × 1.7 = 5.1 mg → However, the upper limit is 4.5 mg; therefore, 4.5 mg is administered.