Instructions for Melphalan/Melphalan for Injection

1. Common name: Melphalan for injection, Melphalan flufenamide

Product name: Melphalan, Pepaxti

2. Indications:

Melphalan for Injection/Melphalan flufenamide is indicated in combination with dexamethasone for the treatment of adult patients with relapsed or refractory (R/R) multiple myeloma (MM) who have received at least four prior therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.

3. Usage and dosage:

1. Recommended dose: The recommended dose of melphalan for injection is 40 mg, administered intravenously within 30 minutes on day 1 of each 28-day cycle until disease progression or unacceptable toxicity. Dexamethasone 40 mg was administered orally or intravenously on days 1, 8, 15, and 22 of each cycle. For patients 75 years of age or older, reduce the dexamethasone dose to 20 mg.

2. Recommended premedication and concomitant medication: Consider providing 5-hydroxytryptamine-3 (5-HT3) receptor antagonists or other antiemetics before and during treatment with injectable melphalan.

3. Dose adjustment: During treatment with melphalan for injection, adverse reactions may occur. The doctor will adjust the drug dose according to the severity of the condition. Intravenous administration is given on the first day of every 28-day cycle. The first dose can be reduced to 30 mg; the second dose can be reduced to 20 mg. For patients who cannot tolerate 20 mg, melphalan treatment should be permanently discontinued.

4. Adverse reactions:

In clinical studies of melphalan for injection, the most common side effects (≥20%) were fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection, and the most common laboratory abnormalities (≥50%) were leukopenia, thrombocytopenia, lymphopenia, neutropenia, hemoglobin decrease, and creatinine increase.

5. Supply and storage:

Melphalan for injection is a white to light white lyophilized powder for reconstitution(After reconstitution, the solution is clear and colorless to light yellow. Each 50mL single-dose vial contains 20mg of melphalan. Each 20mg vial is packed in a single carton. It needs to be refrigerated at 2°C to 8°C (36°F to 46°F) and protected from light. Store it in the original carton until use.

6. Taboo:

Injectable melphalan is contraindicated in patients with a history of severe allergic reaction to Melphalan flufenamide or melphalan.

7. Mechanism of action:

Melphalan flufenamide is a peptide conjugated alkylating agent. Due to its lipophilicity, Melphalan flufenamideis passively distributed into cells and is then enzymatically hydrolyzed to melphalan. Similar to other nitrogen mustard drugs, cross-linking of DNA is related to the anti-tumor activity of Melphalan flufenamide. In cell-based experiments, Melphalan flufenamide inhibited proliferation and induced apoptosis of hematopoietic cells and solid tumor cells. Furthermore, Melphalan flufenamide showed synergistic cytotoxicity with dexamethasone in melphalan-resistant and non-resistant multiple myeloma cell lines.

8. Special groups:

Melphalan is a genotoxic drug, therefore verify the pregnancy status of females of childbearing potential before initiating treatment with injectable melphalan; advise females of childbearing potential to use effective contraception during treatment and for 6 months after the last dose; advise men of childbearing potential to use effective contraception during treatment and for 3 months after the last dose; advise women not to breastfeed during treatment and for 1 week after the last dose.