Multiple Myeloma – Conditioning Treatment: Melphalan is indicated as a high-dose conditioning therapy prior to hematopoietic progenitor (stem) cell transplantation in patients with multiple myeloma.

Melphalan is an alkylating agent of the bischloroethylamine type. Its cytotoxic effect is mainly due to cross-linking of DNA strands, likely by binding to the N7 position of guanine. Like other bifunctional alkylating agents, it is effective against both resting and rapidly dividing tumor cells.

Recommended Dosage for Conditioning Treatment: The recommended dose of Melphalan is 100 mg/m²/day given as a 30-minute intravenous infusion for 2 consecutive days (Day -3 and Day -2) prior to autologous stem cell transplantation (ASCT, Day 0). In patients weighing more than 130% of their ideal body weight, body surface area should be calculated using adjusted ideal body weight.

No formal drug interaction studies have been conducted. Severe renal impairment has been reported in patients receiving a single intravenous dose of melphalan (140–250 mg/m²) followed by standard oral doses of cyclosporine. Intravenous melphalan may also lower the threshold for BCNU-induced lung toxicity.

History of serious allergic reaction to melphalan.

The most common adverse reactions (≥50% patients) include decreased neutrophil count, decreased white blood cell count, decreased lymphocyte count, decreased platelet count, diarrhea, nausea, fatigue, hypokalemia, anemia, and vomiting.

Based on its mechanism of action, Melphalan can cause fetal harm, including teratogenicity and embryo-fetal lethality, when given during pregnancy. It is a genotoxic drug and may cause chromosomal damage in humans. Animal studies have shown embryo-lethality and teratogenic effects at doses lower than clinical doses. Pregnant women should be informed about the potential risks to the fetus. While specific background risks are unknown, in the general population, the risk of major birth defects is 2–4% and miscarriage is 15–20%.

It is not known whether melphalan is excreted in human milk. Because many drugs are excreted in human milk and due to the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment with Melphalan and for 1 week after the last dose.

Bone Marrow Suppression: In patients receiving Melphalan as part of a conditioning regimen, myeloablation occurs in all cases. Do not initiate conditioning if stem cell support is unavailable for rescue. Monitor complete blood counts and provide supportive care for infections, anemia, and thrombocytopenia until adequate hematopoietic recovery occurs.

Gastrointestinal Toxicity: Nausea, vomiting, mucositis, and diarrhea occur in more than 50% of patients receiving Melphalan in conditioning regimens. Use prophylactic antiemetics and provide supportive care. Severe (Grade 3/4) mucositis has been reported; ensure adequate nutritional support and pain management in affected patients.

Hepatotoxicity: Liver abnormalities ranging from elevated liver enzymes to clinical hepatitis and jaundice have been reported. Hepatic veno-occlusive disease may also occur. Monitor liver function tests regularly.

Hypersensitivity: Acute hypersensitivity reactions, including anaphylaxis, have occurred in about 2% of patients receiving intravenous Melphalan. Symptoms may include urticaria, itching, edema, rash, tachycardia, bronchospasm, dyspnea, and hypotension. Discontinue Melphalan in case of severe reactions.

Secondary Malignancies: Melphalan can cause chromosomal damage and has been associated with secondary malignancies such as myeloproliferative disorders and acute leukemia. Weigh the long-term risks against the therapeutic benefits.

Embryo-Fetal Toxicity: Based on its mechanism, Melphalan may cause fetal harm. It is genotoxic and affects rapidly dividing cells. Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose. Males with female partners of reproductive potential should use contraception during treatment and for 3 months after the last dose.

Infertility: Melphalan may impair fertility. In premenopausal women, ovarian suppression leading to amenorrhea has been reported. Reversible or irreversible testicular suppression may also occur in males.

Pediatric Use: Pediatric patients were not included in clinical studies. The safety and effectiveness of melphalan in pediatric patients have not been established.

Geriatric Use: In a single-arm pivotal study of melphalan, 30% of patients were aged 65 years and older, with no patients aged 75 years or above. No overall differences in safety or effectiveness were observed compared to younger patients. However, a higher incidence of engraftment syndrome was noted in older patients: 7% (3/43) in those under 65 years versus 28% (5/18) in those aged 65 years and above.

Fatal overdoses have been reported with melphalan. Overdose symptoms (up to 290 mg/m²) include severe nausea and vomiting, decreased consciousness, convulsions, muscular paralysis, and cholinomimetic effects. High doses (>100 mg/m²) may also cause severe mucositis, stomatitis, colitis, diarrhea, and gastrointestinal bleeding. Elevations in liver enzymes and veno-occlusive disease are uncommon. Significant hyponatremia due to inappropriate ADH secretion has been observed. Nephrotoxicity and adult respiratory distress syndrome have been rarely reported.

The primary toxic effect is bone marrow suppression, leading to leukopenia, thrombocytopenia, and anemia. Hematologic parameters should be closely monitored for 3 to 6 weeks. Limited evidence suggests that autologous bone marrow support or hematopoietic growth factors (e.g., sargramostim, filgrastim) may shorten pancytopenia duration. Supportive care, including blood transfusions and antibiotics, should be provided as needed. Melphalan is not significantly removed by hemodialysis or hemoperfusion. A pediatric case survived a 254 mg/m² overdose with standard supportive care.

Cytotoxic Chemotherapy.

Store Melphalan at 25°C room temperature. Temperature excursions between 15°C to 30°C are permitted. Protect from light and keep it in the original carton until use. Melphalan is a hazardous drug, so special handling and disposal procedures should be followed.