Melflufen
Melflufen Uses, Dosage, Side Effects, Food Interaction and all others data.
Melflufen, also known as melflufen or J1, is a prodrug of melphalan. Melflufen is more readily uptaken by cells than melphalan, and is cleaved to the active metabolite by aminopeptidases. In vitro models show that melphalan is 10 to hundreds of times more potent than melphalan. The increased potency makes melphalan flufenamide a treatment option for patients with relapsed or refractory multiple myeloma who have attempted at least 4 lines of therapy already.
Melflufen was granted FDA approval on 26 February 2021.
Melflufen is an alkylating agent indicated to treat relapsed or refractory multiple myeloma in Melflufen has a long duration of action as it is given every 28 days. Patients should be counselled regarding risks of thrombocytopenia, neutropenia, anemia, infections, secondary malignancies, embryo-fetal toxicity.
| Trade Name | Melflufen |
| Generic | Melphalan flufenamide |
| Melphalan flufenamide Other Names | Melflufen, Melphalan flufenamide, MFF |
| Type | |
| Formula | C24H30Cl2FN3O3 |
| Weight | Average: 498.42 Monoisotopic: 497.1648254 |
| Protein binding | Data regarding the protein binding of melphalan flufenamide are not readily available. However, free melphalan is 60% bound to albumin, 20% bound to alpha-1-acid glycoprotein, and 10% bound to other proteins in plasma. |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Melflufen is a melphalan prodrug used to treat relapsed or refractory multiple myeloma.
Melflufen is indicated in combination with dexamethasone to treat adults with relapsed or refractory multiple myeloma who have received ≥4 therapies and are refractory to at least one proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody.
Melflufen is also used to associated treatment for these conditions: Relapsed Or Refractory Multiple Myeloma
How Melflufen works
Melflufen is a more lipophilic prodrug of melphalan, which allows it to be more readily uptaken by cells. It is likely taken up into malignant cells by passive diffusion, where it is hydrolyzed by aminopeptidase N. The expression of aminopeptidases, along with other hydrolytic enzymes, is upregulated in many malignant cells, making the hydrolysis reaction to melphalan more favourable in a malignant cell. Increased concentrations of free melphalan in malignant cells leads to rapid irreversible DNA damage and apoptosis, reducing the potential for the development of resistance.
Free melphalan is an nitrogen mustard derivative alkylating agent. Melphalan attaches alkyl groups to the N-7 position of guanine and N-3 position of adenine, leading to the formation of monoadducts, and DNA fragmenting when repair enzymes attempt to correct the error. It can also cause DNA cross-linking from the N-7 position of one guanine to the N-7 position of another, preventing DNA strands from separating for synthesis or transcription. Finally, melphalan can induce a number of different mutations. While melphalan induces phosphorylation of the DNA damage marker γ-H2AX in melphalan sensitive cells at 6 hours, melphalan flufenamide induces γ-H2AX at 2 hours. Melflufen is also able to induce γ-H2AX in melphalan-resistant cells.
Toxicity
Data regarding overdoses of melphalan flufenamide are not readily available. However, nonclinical safety studies in dogs have shown an increased risk of mortality in subjects receiving higher than recommended doses. Patients should be treated with symptomatic and supportive measures.
Food Interaction
No interactions found.Volume of Distribution
The mean volume of distribution of melphalan flufenamide is 35 L and of melphalan is 76 L.
Elimination Route
For a 40 mg intravenous infusion, the active metabolite reaches a Cmax of 432 ng/mL, with a Tmax of 4-15 minutes, and an AUC of 3143 h*µg/mL.
Half Life
The mean elimination half life of melphalan flufenamide is 2.1 minutes and of melphalan is 70 minutes.
Clearance
The mean clearance of melphalan flufenamide is 692 L/h and of melphalan is 23 L/h.
Elimination Route
Data regarding the route of elimination of melphalan flufenamide are not readily available. Free melphalan undergoes rapid and spontaneous decomposition, complicating studies on the route of elimination. However, it is expected to be mainly renally excreted.
Innovators Monograph
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