Immunomodulatory Drugs in Multiple Myeloma: Mechanisms of Action and Clinical Experience

Over the last two decades, the outcomes for patients with multiple myeloma, a plasma cell malignancy, have dramatically improved. The development of the immunomodulatory drugs (IMiDs), which include thalidomide, lenalidomide, and pomalidomide, has contributed significantly to these improved outcomes...

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Vydáno v:	Drugs (New York, N.Y.) Ročník 77; číslo 5; s. 505 - 520
Hlavní autoři:	Holstein, Sarah A., McCarthy, Philip L.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Cham Springer International Publishing 01.04.2017 Springer Nature B.V
Témata:	Angiogenesis Chemotherapy Cytotoxicity Drug development Drug dosages Drugs FDA approval Health risk assessment Humans Immunologic Factors - therapeutic use Immunomodulation Immunomodulators Internal Medicine Lenalidomide Leprosy Leukemia Malignancy Medical prognosis Medicine Medicine & Public Health Molecular modelling Molecular structure Multiple myeloma Multiple Myeloma - diagnosis Multiple Myeloma - drug therapy Patients Pharmacology/Toxicology Pharmacotherapy Review Article Stem cells Structure-function relationships Studies Thalidomide Thalidomide - analogs & derivatives Thalidomide - therapeutic use Thromboembolism Thrombosis Topical Collection on Immuno-Oncology Transcription factors Transplants & implants Ubiquitination Acute Myeloid Leukemia Bortezomib Natural Killer Cell Myeloma Thalidomide
ISSN:	0012-6667, 1179-1950, 1179-1950
On-line přístup:	Získat plný text
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Shrnutí:	Over the last two decades, the outcomes for patients with multiple myeloma, a plasma cell malignancy, have dramatically improved. The development of the immunomodulatory drugs (IMiDs), which include thalidomide, lenalidomide, and pomalidomide, has contributed significantly to these improved outcomes. While thalidomide is now less commonly prescribed, lenalidomide is widely used in the treatment of newly diagnosed transplant-eligible and transplant-ineligible patients, in the maintenance setting post-transplant and in the relapsed/refractory setting, while pomalidomide is currently utilized in the relapsed/refractory setting. The IMiDs have been reported to have a multitude of activities, including anti-angiogenic, cytotoxic, and immunomodulatory. However, the more recent discoveries that the IMiDs bind to cereblon and thus regulate the ubiquitination of key transcription factors including IKZF1 and IKZF3 have provided greater insight into their mechanism of action. Here, the clinical efficacy of these agents in myeloma is reviewed and the structure-function relationship, the molecular mechanisms of action, and the association of IMiDs with second primary malignancies and thrombosis are discussed.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23
ISSN:	0012-6667 1179-1950 1179-1950
DOI:	10.1007/s40265-017-0689-1