Melphalan (Alkeran) — Clinical FAQs

Question 1

What is Melphalan FDA-approved to treat?

Accepted Answer

Melphalan is FDA-approved for the following oncology indications: 1. Multiple myeloma — palliative treatment (oral; FDA approved 1964); high-dose IV (200 mg/m²) as conditioning for autologous stem cell transplantation (Evomela, FDA approved 2016) 2. Epithelial ovarian carcinoma — palliative treatment (oral; FDA approved).

Question 2

How does Melphalan work (mechanism of action)?

Accepted Answer

Melphalan is a bifunctional phenylalanine mustard alkylating agent that forms highly reactive carbonium ion intermediates via intramolecular cyclization. These intermediates alkylate the N7 position of guanine in DNA, creating interstrand and intrastrand DNA crosslinks that prevent DNA replication and transcription. The drug is cell-cycle nonspecific, acting on both dividing and resting cells. Its structural similarity to phenylalanine allows active transport into cells via amino acid transport systems, contributing to its activity in amino acid-avid tumor cells.

Question 3

How is Melphalan administered?

Accepted Answer

Melphalan is administered Intravenous (IV) or Oral (PO). Oral (palliative MM): 0.

Question 4

What are the most common side effects of Melphalan?

Accepted Answer

The most commonly reported side effects of Melphalan (≥10% incidence) include: Myelosuppression (severe neutropenia, thrombocytopenia, anemia) — dose-dependent, Nausea and vomiting (especially high-dose IV), Mucositis/stomatitis (severe with high-dose regimens), Diarrhea, Alopecia (complete with high-dose) and others (10 total). Consult your oncologist for complete prescribing information.

Question 5

Does Melphalan have a black box warning?

Accepted Answer

Yes. Melphalan carries FDA black box warning(s) regarding: 1. Severe bone marrow suppression with resulting infection and hemorrhage; may be dose-limiting 2. Secondary malignancies (acute myeloid leukemia, myelodysplastic syndrome) reported with prolonged therapy 3. Hypersensitivity reactions including anaphylaxis reported with IV formulation 4. Mutagenic and potentially carcinogenic in humans

Question 6

Is Melphalan safe during pregnancy?

Accepted Answer

Melphalan pregnancy safety: Category D — melphalan is teratogenic and embryotoxic in animals. Should not be used during pregnancy. Women of childbearing potential must use effective contraception during therapy and for at least 6 months afterward.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

Melphalan — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms