Dr. Holstein Discusses Role of Melflufen in Myeloma

Sarah Holstein, MD, PhD
Published: Tuesday, Feb 19, 2019



Sarah Holstein, MD, PhD, associate professor of medicine, University of Nebraska Medical Center, discusses the role of melflufen in the treatment of patients with myeloma.

At its heart, melflufen is related to melphalan, a traditional drug that oncologists have used in the myeloma space for the last 50-plus years. In the United States, although the low-dose form of melphalan is rarely used anymore, it is often used in a high-dose form in the context of stem cell transplant. Melflufen is essentially a pro-drug version of melphalan which takes advantage of the biology of malignant plasma cells, Holstein explains.

Melflufen has a lipophilic component to it. The drug gets readily taken up into the cells, but for it to become active, it needs to first be cleaved by enzymes called aminopeptidases. Myeloma cells express many aminopeptidases, Holstein notes, because it is part of a plasma cell that needs protein and then be able to degrade protein, so that more proteins can be produced. As a result of myeloma cells having high levels of aminopeptidases, they then cleave the melflufen into the active alkylating moiety, which essentially gets trapped inside the cell where it can act as an alkylating agent.

Melflufen is an interesting way to more effectively deliver high concentrations of an active alkylator agent more selectively to myeloma cells, and, therefore, avoid some of the toxicity that is often seen with higher doses of melphalan, she concludes.
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Sarah Holstein, MD, PhD, associate professor of medicine, University of Nebraska Medical Center, discusses the role of melflufen in the treatment of patients with myeloma.

At its heart, melflufen is related to melphalan, a traditional drug that oncologists have used in the myeloma space for the last 50-plus years. In the United States, although the low-dose form of melphalan is rarely used anymore, it is often used in a high-dose form in the context of stem cell transplant. Melflufen is essentially a pro-drug version of melphalan which takes advantage of the biology of malignant plasma cells, Holstein explains.

Melflufen has a lipophilic component to it. The drug gets readily taken up into the cells, but for it to become active, it needs to first be cleaved by enzymes called aminopeptidases. Myeloma cells express many aminopeptidases, Holstein notes, because it is part of a plasma cell that needs protein and then be able to degrade protein, so that more proteins can be produced. As a result of myeloma cells having high levels of aminopeptidases, they then cleave the melflufen into the active alkylating moiety, which essentially gets trapped inside the cell where it can act as an alkylating agent.

Melflufen is an interesting way to more effectively deliver high concentrations of an active alkylator agent more selectively to myeloma cells, and, therefore, avoid some of the toxicity that is often seen with higher doses of melphalan, she concludes.

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TitleExpiration DateCME Credits
Community Practice Connections™: 22nd Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas and MyelomaMay 30, 20192.0
Online Medical Crossfire®: 5th Annual Miami Lung Cancer ConferenceMay 30, 20196.5
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