Recent advances of IMiDs in cancer therapy.
OBJECTIVE
Immunomodulatory derivatives of thalidomide (IMiDs) have been used for the treatment of myelodysplastic syndrome and multiple myeloma; however, the mechanism of action of IMiDs is largely unknown. The purpose of this review is to provide an overview of recent findings on the mechanism of action of IMiDs, its use as a new treatment modality for various hematologic malignancies, and problems associated with stem cell mobilization after lenalidomide treatment.


RESULTS
Recent clinical trials revealed lenalidomide as a promising new agent for the treatment of follicular non-Hodgkin's lymphoma (NHL) and also diffuse large B-cell lymphoma. Pomalidomide was shown to be even more effective in refractory multiple myeloma than lenalidomide. New guidelines for the management of venous thromboembolism have been established. The chemokine receptor 4 (CXCR4) inhibitor, AMD-3100, is recommended for patients who have received lenalidomide and failed to mobilize stem cells after G-SCF and cyclophosphamide. Preclinical studies investigated the pleiotropic functions of IMiDs, with a particular focus on immune modulation, their effects on new targets, stem cells and disruption of plasma cell microenvironment interactions.


CONCLUSIONS
More and more indications for the use of IMiDs in hematologic malignancies have been identified. In order to establish better clinical usage of IMiDs, it is of utmost importance to clarify the antitumor mechanism of IMiDs. Here, we provide a review on the recent advances in the development of IMiDs. New guidelines for venous thromboembolism prophylaxis and stem cell mobilization failure associated with lenalidomide treatment have been established.
Li
Shirong
S
Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Gill
Navkiranjit
N
Lentzsch
Suzanne
S
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D059016:Tumor Microenvironment / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D007155:Immunologic Factors; D013792:Thalidomide