Thalidomide and lenalidomide: Mechanism-based potential drug combinations

Sonia Vallet Division of Hematology and Oncology, Cancer Center, Massachusetts General Hospital, Boston, MA, USA; Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USACorrespondence[email protected]

Antonio Palumbo Cattedra di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Torino, Italy

Noopur Raje Division of Hematology and Oncology, Cancer Center, Massachusetts General Hospital, Boston, MA, USA; Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

Mario Boccadoro Cattedra di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Torino, Italy

Kenneth C. Anderson Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

Abstract

Thalidomide and its analogue lenalidomide are potent anti-inflammatory, anti-angiogenic and immunomodulatory drugs, successfully used for the treatment of hematological cancers, in particular multiple myeloma (MM). Both drugs reveal a dual mechanism of action: they target tumour cells by direct cytotoxicity and, indirectly, by interfering with several components of the bone marrow microenvironment. Lenalidomide and thalidomide are versatile drugs with a broad range of activities that potentiate the anti-MM effects of conventional and novel agents. Here, we review the mechanism of action of these drugs, providing a rationale for combination studies in order to improve patient outcome and reduce side effects.

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