Mechanistic and Clinical Aspects of Lenalidomide Treatment for Chronic Lymphocytic Leukemia

There have been significant advances in our understanding of the pathogenesis of chronic lymphocytic leukemia (CLL) over the last decade, which has been accompanied by a rapid increase in treatment options. Inhibitors of BCRsignaling such as ibrutinib and idelalisib, and pro-apoptotic agents such as ABT- 199 have shown great promise in initial clinical trials and have been at the forefront of recent developments. However, despite the encouraging early data, these agents do not appear to represent a "cure" for CLL and mechanisms of resistance to these agents have already been identified. In light of these considerations there remains a need for alternative treatment strategies. Lenalidomide, a second-generation derivative of thalidomide, has been demonstrated to have significant clinical activity in CLL. Its effect appears to be mediated by reduction of CLL-cell proliferation, improvement of anti-tumor immune responses and reduction of pro-tumoral factors in the CLL microenvironment. This review discusses our current understanding of the mechanism of action of lenalidomide on both healthy cells and in CLL. It also summarises the published clinical trial experience with this drug, and proposes an ongoing role for this agent in the CLL armamentarium.