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Published on: July 31, 2016
Melflufen for relapsed and refractory multiple myeloma
Albert Oriol1, Alessandra Larocca2, Xavier Leleu3
1Institut Josep Carreras and Institut Català d'Oncologia, Hospital Germans Trias I Pujol , Badalona, Spain.
Introduction:
The overall survival of patients with multiple myeloma has improved with the advent of novel agents; however, multiple myeloma remains incurable. Combinations of standard-of-care agents such as immunomodulators, proteasome inhibitors, and anti-CD38 monoclonal antibodies are increasingly used in earlier lines of therapy. Patients with disease that is refractory to multiple novel agents represent a population with high unmet medical need and for whom therapies with new mechanisms of action could be beneficial. Melphalan flufenamide (melflufen) has demonstrated encouraging activity in patients with relapsed and refractory multiple myeloma.
Areas Covered:
This review provides an overview of the mechanism of action of melflufen, a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly delivers alkylating agents into tumor cells. It reviews key Phase I and II clinical trial data for melflufen in combination with dexamethasone as well as in triplet combinations with daratumumab or bortezomib. The safety profile of melflufen, which is characterized primarily by clinically manageable hematologic adverse events, is described.
Expert Opinion:
Melflufen has potential to fill a gap in the myeloma treatment landscape by providing a new mechanism of action with clinically meaningful efficacy and a favorable safety profile in patients refractory to multiple novel agents.
Insights
Melphalan flufenamide (melflufen) shows promise for treating relapsed or refractory multiple myeloma. This novel peptide-drug conjugate offers a new mechanism of action and a manageable safety profile for patients with limited options.
Area of Science:
- Oncology
- Hematology
- Pharmacology
Background:
- Multiple myeloma survival has improved but remains incurable.
- Novel agents are increasingly used, creating a need for new mechanisms of action in refractory disease.
- Melphalan flufenamide (melflufen) shows activity in relapsed/refractory multiple myeloma.
Purpose of the Study:
- To review the mechanism of action of melflufen.
- To summarize clinical trial data for melflufen in combination therapies.
- To describe the safety profile of melflufen.
Main Methods:
- Review of melflufen's mechanism as a peptide-drug conjugate.
- Analysis of Phase I and II clinical trial data.
- Evaluation of safety data, focusing on adverse events.
Main Results:
- Melflufen targets aminopeptidases, delivering alkylating agents to tumor cells.
- Clinical trials investigated melflufen with dexamethasone, daratumumab, or bortezomib.
- The safety profile is mainly characterized by manageable hematologic adverse events.
Conclusions:
- Melflufen offers a new mechanism of action for multiple myeloma treatment.
- It demonstrates clinically meaningful efficacy in patients refractory to multiple novel agents.
- Melflufen presents a favorable safety profile, addressing an unmet medical need.
