, Volume 77, Issue 5, pp 505–520 | Cite as

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

  • Sarah A. Holstein
  • Philip L. McCarthyEmail author
Review Article
Part of the following topical collections:
  1. Topical Collection on Immuno-Oncology


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.


Natural Killer Cell Acute Myeloid Leukemia Myeloma Thalidomide Bortezomib 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Compliance with Ethical Standards


No funding was received for the preparation of this manuscript.

Conflict of interest

S.A.H. has served on advisory committees for Celgene, Takeda, and Amgen and has received consulting fees from Celgene; P.L.M. has received honoraria from Bristol-Myers Squibb, Celgene, Sanofi-Aventis, Takeda, and Binding Site; research funding from Celgene; and has served on advisory committees/review panels/board membership for Bristol-Myers Squibb, Celgene, Sanofi-Aventis, Takeda, Binding Site, and Karyopharm.


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Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Division of Oncology and Hematology, Department of Internal MedicineUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Department of MedicineBlood and Marrow Transplant Center, Roswell Park Cancer InstituteBuffaloUSA

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