Instructions for Mirvetuximab soravtansine-gynx

1. Name: Mirvetuximab, Mirvetuximab soravtansine-gynx, Elahere

2. Indications:

Mirvetuximab soravtansine-gynx (Mirvetuximab soravtansine-gynx) is indicated for adult patients with folate receptor-alpha (FR-alpha)-positive, platinum-resistant epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have received one to three prior systemic therapies.

3. Usage and dosage:

1. Before treatment: Doctors will choose to use mivituximab to treat patients with platinum-resistant epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer based on the presence of FR-α tumor expression in the patient's body. Before initiating mivituximab and every other cycle for the first 8 cycles, perform ophthalmic examinations, including visual acuity and slit-lamp examination, as clinically indicated.

2. Recommended dose: The recommended dose of milvituximab is 6 mg/kg adjusted ideal body weight (AIBW), intravenously infused once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity occurs.

The total dose of milvituximab was calculated based on each patient's AIBW using the following formula:

AIBW=ideal body weight (IBW[kg])+0.4*(Actual weight[kg]-IBW);

FemaleIBW（kg）=0.9 *Height（cm）-92.

3. Dose adjustment: If a patient experiences adverse reactions after using mivituximab, doctors will adjust the dose as follows; the first dose will be reduced to 5 mg/kg of adjusted ideal body weight (AIBW); the second dose will be reduced to 4 mg/kg of adjusted ideal body weight (AIBW); patients who cannot tolerate 4 mg/kg AIBW should permanently discontinue the drug.

4. Management:

(1) Premedication: One day before each infusion of milvituximab, the doctor may give premedication, including corticosteroids, antihistamines, antipyretics, antiemetics, etc., to reduce infusion-related reactions (IRRs), incidence and severity of nausea and vomiting.

(2) Eye Care: Initial prescription and renewal of any corticosteroid medication should be done only after examination with a slit lamp. Apply one drop of topical ophthalmic steroid to each eye 6 times daily through day 4, beginning the day before each infusion; then administer one drop to each eye 4 times daily on days 5-8 of each mivituximab cycle. It is recommended to use lubricating eye drops at least four times daily during treatment with milvituximab. Instruct patients to use lubricating eye drops and recommend waiting at least 10 minutes after administration of topical ocular steroids before instilling lubricating eye drops.

4. Adverse reactions:

In clinical studies of mivituximab, the most common (≥20%) adverse reactions (including laboratory abnormalities) included visual impairment, fatigue, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, keratopathy, abdominal pain, lymphopenia, peripheral neuropathy, diarrhea, decreased albumin, constipation, increased alkaline phosphatase, dry eye, decreased magnesium, leukopenia, neutropenia, and hemoglobinopenia.

5. Storage:

Mivituximab is an injectable formulation. Typically, vials of milvituximab are stored upright in a refrigerator at 2°C to 8°C (36°F to 46°F) until preparation in the original carton to avoid light. Do not freeze or shake.

If the diluted milvituximab infusion solution is not used immediately, store the solution at ambient temperature[(18°C to 25°C (64.4°F to 77°F)]] for no more than 8 hours (including infusion time), or refrigerate at 2°C to 8°C (36°F to 46°F) for no more than 12 hours. If refrigerated, allow the infusion bag to come to room temperature before administration. After refrigeration, give the diluted infusion within 8 hours, including the time of infusion.

6. Special groups:

Based on its mechanism of action, milvituximab can cause embryo-fetal damage when administered to pregnant women because it contains a genotoxic compound (DM4) and affects actively dividing cells. Therefore, it is recommended that women should not breastfeed during milvituximab treatment and for 1 month after the last dose; for women of reproductive potential, use effective contraception during milvituximab treatment and for 7 months after the last dose.

7. Mechanism of action:

Mivituximab is an antibody-drug conjugate (ADC) against the folate receptorα (FR-α)ChimericIgG1. The small molecule DM4 is a microtubule inhibitor linked to antibodies via a cleavable linker. Upon binding to folate receptor alpha, mivituximab is internalized and subsequently released intracellularly by proteolytic cleavage of DM4. DM4 disrupts the intracellular microtubule network, leading to cell cycle arrest and apoptotic cell death.