Relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib

Relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib

Ajay Nooka, Charise Gleason, Daniela Casbourne, Sagar LonialDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta GA, USAAbstract: Proteasomal inhibition revolutionized myeloma therapies in this decade of novel agents. The only US Food...

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Autores principales: Nooka A, Gleason C, Casbourne D, Lonial S
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2013
Materias:
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/5e8547a85bf649f98dcb50178e8dd7cd
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spelling oai:doaj.org-article:5e8547a85bf649f98dcb50178e8dd7cd2021-12-02T00:22:26ZRelapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib1177-54751177-5491https://doaj.org/article/5e8547a85bf649f98dcb50178e8dd7cd2013-01-01T00:00:00Zhttp://www.dovepress.com/relapsed-and-refractory-lymphoid-neoplasms-and-multiple-myeloma-with-a-a12091https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Ajay Nooka, Charise Gleason, Daniela Casbourne, Sagar LonialDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta GA, USAAbstract: Proteasomal inhibition revolutionized myeloma therapies in this decade of novel agents. The only US Food and Drug Administration approved proteasome inhibitor so far, bortezomib effectively targets the constitutive proteasome subunit ß5 of the 26S proteasome. Bortezomib induces high and quality response rates that are durable. However, myeloma cells acquire resistance to bortezomib through various mechanisms. Further, grade 3/4 peripheral neuropathy is seen in up to a quarter of patients treated with bortezomib. While the recent change in the mode of administration via the subcutaneous route is associated with a lower incidence of grade 3/4 peripheral neuropathy, it remains a major concern. The second generation proteasome inhibitors are promising, with increased preclinical efficacy and a better administration schedule. The current review spotlights the second generation proteasome inhibitors with special focus on the safety and efficacy of carfilzomib, an epoxyketone with lesser peripheral neuropathy, which exhibits irreversible proteasome inhibition. In this article, we review the pharmacology and preclinical and clinical efficacy and safety of carfilzomib alone and in combination with other chemotherapeutic agents in the various lymphoid neoplasms and multiple myeloma as well as ongoing clinical trials.Keywords: myeloma, carfilzomib, second generation, proteasome inhibitor, epoxyketoneNooka AGleason CCasbourne DLonial SDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2013, Iss default, Pp 13-32 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Nooka A
Gleason C
Casbourne D
Lonial S
Relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib
description Ajay Nooka, Charise Gleason, Daniela Casbourne, Sagar LonialDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta GA, USAAbstract: Proteasomal inhibition revolutionized myeloma therapies in this decade of novel agents. The only US Food and Drug Administration approved proteasome inhibitor so far, bortezomib effectively targets the constitutive proteasome subunit ß5 of the 26S proteasome. Bortezomib induces high and quality response rates that are durable. However, myeloma cells acquire resistance to bortezomib through various mechanisms. Further, grade 3/4 peripheral neuropathy is seen in up to a quarter of patients treated with bortezomib. While the recent change in the mode of administration via the subcutaneous route is associated with a lower incidence of grade 3/4 peripheral neuropathy, it remains a major concern. The second generation proteasome inhibitors are promising, with increased preclinical efficacy and a better administration schedule. The current review spotlights the second generation proteasome inhibitors with special focus on the safety and efficacy of carfilzomib, an epoxyketone with lesser peripheral neuropathy, which exhibits irreversible proteasome inhibition. In this article, we review the pharmacology and preclinical and clinical efficacy and safety of carfilzomib alone and in combination with other chemotherapeutic agents in the various lymphoid neoplasms and multiple myeloma as well as ongoing clinical trials.Keywords: myeloma, carfilzomib, second generation, proteasome inhibitor, epoxyketone
format article
author Nooka A
Gleason C
Casbourne D
Lonial S
author_facet Nooka A
Gleason C
Casbourne D
Lonial S
author_sort Nooka A
title Relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib
title_short Relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib
title_full Relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib
title_fullStr Relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib
title_full_unstemmed Relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib
title_sort relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/5e8547a85bf649f98dcb50178e8dd7cd
work_keys_str_mv AT nookaa relapsedandrefractorylymphoidneoplasmsandmultiplemyelomawithafocusoncarfilzomib
AT gleasonc relapsedandrefractorylymphoidneoplasmsandmultiplemyelomawithafocusoncarfilzomib
AT casbourned relapsedandrefractorylymphoidneoplasmsandmultiplemyelomawithafocusoncarfilzomib
AT lonials relapsedandrefractorylymphoidneoplasmsandmultiplemyelomawithafocusoncarfilzomib
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