gemtuzumab

Generic name: gemtuzumab

Trade name: MYLOTARG

All names: gemtuzumab, gemtuzumab, gemtuzumab ozogamicin, MYLOTARG

Indications:

For adults with newly diagnosed myeloid cell differentiation antigen (CD33)-positive AML (acute myeloid leukemia)

For adults and children ≥2 years of age with relapsed/refractory myeloid cell differentiation antigen (CD3) 3) Positive AML (acute myeloid leukemia)

Usage and dosage:

Specification: 5mg

Adult newly diagnosed CD33-positive AML

Combination regimen

Induction cycle: Combined with daunorubicin and cytarabine on days 1, 4 and 7, intravenously for 3 mg /m² (up to one 4.5 mg vial)

For patients requiring a second induction cycle, do not use gemtuzumab during the second induction cycle

Concomitant: 3 mg/m² intravenously on day 1 (up to 1 4.5 mg vial) mg vial), in combination with daunorubicin and cytarabine

Monotherapy

The treatment course consists of 1 induction cycle and up to 8 cycles of continuous treatment

Induction: 6 mg/m² intravenously on day 1, 3 mg/m² intravenously on day 8

Continuation treatment: 2 mg intravenous infusion on day 1 of week 4 /m²

Relapsed or refractory CD33-positive AML

3 mg on days 1, 4 and 7 /m², 1 cycle in total

Adverse reactions:

> 10% (new diagnosis plus daunorubicin and cytarabine)

Hypophosphatemia, grade 3 or higher (64%)

Hypokalemia, grade 3 or higher (57%)

Grade 3 or higher infection (47-55%)

Hyponatremia, grade 3 or higher (44%)

Prolonged thrombocytopenia (19-35%)

Grade 3 or higher bleeding (5-18%)

Increased AST, grade 3 or higher (14%)

Elevated alkaline phosphatase, grade 3 or higher (13%)

> 10% (relapse on monotherapy)

Fever, all grades (79%)

Infection at all grades (42%)

AST increased in all grades (40%)< /p>

Bleeding, all grades (23%)

Nausea and vomiting, all grades (21%)

Constipation, all grades (21%)

Mucositis, all grades (21 %)

Headache of all grades (19%)

Elevated ALT of all grades (16%)

Rush, all grades (16%)

Sepsis grade 3 ( 32%)

Fever in Grade 3 (16%)

Rash in Grade 3 (11%)

1-10% (new diagnosis plus daunorubicin and cytarabine)

ALT elevated, grade 3 or higher (10%)

Blood bilirubin elevated, grade 3 or higher (8%)

Long-term neutropenia (2-3%)

Veno-occlusive disease, grade 3 or higher (2%)

1-10% (relapse on monotherapy)

Hyperbilirubinemia (7%)

Grade 3 pulmonary inflammation (7%)

Grade 3 bleeding (7%)

Mucositis grade 3 (4%)

Grade 3 pain (4%)

Diarrhea grade 3 (2%)

Grade 3 Headache (2%)

Tachycardia, grade 3 (2%)

Grade 3 pulmonary edema (2%)

Contraindications:

Hypersensitivity to gemtuzumab or any of its components or the active substance in any excipient

Precautions:

Hepatotoxicity, including severe or fatal VOD, also known as SOS, has been reported.

For patients receiving gemtuzumab in combination with daunorubicin and cytarabine for newly diagnosed de novo AML, when cytogenetic test results are available, consider whether the potential benefits of continued treatment outweigh the risks to the individual patient

Animal data report that gemetuzumab may cause embryofetal harm when administered to pregnant women;

Infusion phase Concerned Reactions

Life-threatening or fatal infusion-related reactions may occur during or within 24 hours after gemtuzumab infusion

Drug therapy prior to gemtuzumab infusion

Frequent monitoring of vital signs during infusion

Patients suspected of infusion-related reactions, especially dyspnea, bronchospasm, or hypotension, should Interrupt the infusion immediately

Monitor the patient during or for ≥1 hour after completion of the infusion or until complete resolution of symptoms

Discontinue gemtuzumab in patients who develop signs or symptoms of an allergic reaction (e.g., severe respiratory symptoms or clinically significant hypotension)

Bleeding

Fatal or fatal thrombocytopenia The risk of life-threatening bleeding

The proportion of patients with persistent thrombocytopenia increases with the stage of progressive treatment and is higher in patients treated with gemtuzumab than in patients treated with chemotherapy alone

Assess blood cell counts before each dose of gemtuzumab; monitor frequently after treatment until cytopenias occur

Monitor patients during treatment Signs/symptoms of bleeding; treat severe bleeding, hemorrhage, or persistent thrombocytopenia by discontinuing treatment and providing appropriate medical care

QT interval prolongation

QT interval prolongation has been observed in patients receiving other calicheamicin-containing drugs

Have a history or susceptibility to QTc prolongation and are taking medications known to prolong In patients with QT intervals or on medications with electrolyte disorders, obtain ECG and electrolytes as needed before starting medication and during treatment

Storage:

Protect from light

Do not freeze

Unopened vials

Store in original carton at 2-8°C (3 Refrigerated at 6-46°F)

Reconstituted solution

Can be refrigerated at 2-8°C (36-46°F) for up to 1 hour

Dilute solution

Can be stored at room temperature 15-25°C (59-77°F) for up to 6 hours; the 6-hour time frame includes a 2-hour infusion time and 1 hour if needed Required) to allow refrigerated diluted solutions to equilibrate to room temperature

Can be refrigerated at 2-8°C (36-46°F) for up to 12 hours, including up to 1 hour in the reconstituted vial

Mechanism of action:

CD33-directed antibody-drug conjugates (ADCs); The antibody moiety (hP67.6) recognizes the human CD33 antigen, and the small molecule N-acetyl gamma calicheamicin is a cytotoxic agent that is covalently attached to the antibody via a linker

Non-clinical data suggest that anticancer activity is a result of ADC binding to CD33-expressing tumor cells, subsequent internalization of the ADC-CD33 complex, and intracellular release of N-acetyl calicheamicin dimethyl hydrazide via hydrolytic cleavage of the linker.

Activation of N-acetyl gamma calicheamicin dimethylhydrazine induces double-stranded DNA breaks and subsequently induces cell cycle arrest and apoptotic cell death

Efficacy and Safety:

AML-19 is a multicenter, randomized, open-label phase 3 clinical trial comparing single-agent Mylotarg (Gemtuzumab ozogamicin/gemtuzumab) (n = 118) with best supportive care (n = 119) in elderly patients who cannot tolerate other AML treatments. As initial treatment, patients received MYLOTARG 6 mg/m2 on Day 1 and MYLOTARG 3 mg/m2 on Day 8. As continuation therapy, patients without evidence of disease progression received MYLOTARG 2 mg/m2 on Day 1, every four weeks. The efficacy of MYLOTARG is based on a significant improvement in overall survival (OS). Median OS was 4.9 months for patients who received MYLOTARG compared with 3.6 months for patients who received best supportive care (HR = 0.69 [95% CI: 0.53-0.90] [2-sided p = 0.005]).