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Melflufen: A Peptide–Drug Conjugate for the Treatment of Multiple Myeloma

Despite the availability of new therapies that have led to improved outcomes for patients with multiple myeloma, most patients will eventually relapse. With triplet and even quadruplet combination therapies becoming standard in the first and second line, many patients will have few treatment options...

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Autores principales: Mateos, María-Victoria, Bladé, Joan, Bringhen, Sara, Ocio, Enrique M, Efebera, Yvonne, Pour, Luděk, Gay, Francesca, Sonneveld, Pieter, Gullbo, Joachim, Richardson, Paul G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601491/
https://www.ncbi.nlm.nih.gov/pubmed/32992506
http://dx.doi.org/10.3390/jcm9103120
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author Mateos, María-Victoria
Bladé, Joan
Bringhen, Sara
Ocio, Enrique M
Efebera, Yvonne
Pour, Luděk
Gay, Francesca
Sonneveld, Pieter
Gullbo, Joachim
Richardson, Paul G.
author_facet Mateos, María-Victoria
Bladé, Joan
Bringhen, Sara
Ocio, Enrique M
Efebera, Yvonne
Pour, Luděk
Gay, Francesca
Sonneveld, Pieter
Gullbo, Joachim
Richardson, Paul G.
author_sort Mateos, María-Victoria
collection PubMed
description Despite the availability of new therapies that have led to improved outcomes for patients with multiple myeloma, most patients will eventually relapse. With triplet and even quadruplet combination therapies becoming standard in the first and second line, many patients will have few treatment options after second-line treatment. Melflufen (melphalan flufenamide) is a first-in-class peptide–drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. Once inside the tumor cells, melflufen is hydrolyzed by peptidases to release alkylator molecules, which become entrapped. Melflufen showed anti-myeloma activity in myeloma cells that were resistant to bortezomib and the alkylator melphalan. In early phase studies (O-12-M1 and HORIZON [OP-106]), melflufen plus dexamethasone has demonstrated encouraging clinical activity and a manageable safety profile in heavily pretreated patients with relapsed/refractory multiple myeloma, including those with triple-class refractory disease and extramedullary disease. The Phase III OCEAN study (OP-104) is further evaluating melflufen plus dexamethasone in patients with relapsed/refractory multiple myeloma. The safety profile of melflufen is characterized primarily by clinically manageable hematologic adverse events. Melflufen, with its novel mechanism of action, has the potential to provide clinically meaningful benefits to patients with relapsed/refractory multiple myeloma, including those with high unmet needs.
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spelling pubmed-76014912020-11-01 Melflufen: A Peptide–Drug Conjugate for the Treatment of Multiple Myeloma Mateos, María-Victoria Bladé, Joan Bringhen, Sara Ocio, Enrique M Efebera, Yvonne Pour, Luděk Gay, Francesca Sonneveld, Pieter Gullbo, Joachim Richardson, Paul G. J Clin Med Review Despite the availability of new therapies that have led to improved outcomes for patients with multiple myeloma, most patients will eventually relapse. With triplet and even quadruplet combination therapies becoming standard in the first and second line, many patients will have few treatment options after second-line treatment. Melflufen (melphalan flufenamide) is a first-in-class peptide–drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. Once inside the tumor cells, melflufen is hydrolyzed by peptidases to release alkylator molecules, which become entrapped. Melflufen showed anti-myeloma activity in myeloma cells that were resistant to bortezomib and the alkylator melphalan. In early phase studies (O-12-M1 and HORIZON [OP-106]), melflufen plus dexamethasone has demonstrated encouraging clinical activity and a manageable safety profile in heavily pretreated patients with relapsed/refractory multiple myeloma, including those with triple-class refractory disease and extramedullary disease. The Phase III OCEAN study (OP-104) is further evaluating melflufen plus dexamethasone in patients with relapsed/refractory multiple myeloma. The safety profile of melflufen is characterized primarily by clinically manageable hematologic adverse events. Melflufen, with its novel mechanism of action, has the potential to provide clinically meaningful benefits to patients with relapsed/refractory multiple myeloma, including those with high unmet needs. MDPI 2020-09-27 /pmc/articles/PMC7601491/ /pubmed/32992506 http://dx.doi.org/10.3390/jcm9103120 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mateos, María-Victoria
Bladé, Joan
Bringhen, Sara
Ocio, Enrique M
Efebera, Yvonne
Pour, Luděk
Gay, Francesca
Sonneveld, Pieter
Gullbo, Joachim
Richardson, Paul G.
Melflufen: A Peptide–Drug Conjugate for the Treatment of Multiple Myeloma
title Melflufen: A Peptide–Drug Conjugate for the Treatment of Multiple Myeloma
title_full Melflufen: A Peptide–Drug Conjugate for the Treatment of Multiple Myeloma
title_fullStr Melflufen: A Peptide–Drug Conjugate for the Treatment of Multiple Myeloma
title_full_unstemmed Melflufen: A Peptide–Drug Conjugate for the Treatment of Multiple Myeloma
title_short Melflufen: A Peptide–Drug Conjugate for the Treatment of Multiple Myeloma
title_sort melflufen: a peptide–drug conjugate for the treatment of multiple myeloma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601491/
https://www.ncbi.nlm.nih.gov/pubmed/32992506
http://dx.doi.org/10.3390/jcm9103120
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