Evidence-based mechanisms of synergy with IMiD agent-based combinations in multiple myeloma

Treatment of multiple myeloma (MM) has seen great advances in recent years, and a key contributor to this change has been the effective use of combination therapies, which have improved both the depth and duration of patient responses. Immunomodulatory drug (IMiD) agents (lenalidomide and pomalidomide) have both tumoricidal and immunostimulatory functions, and due to their multiple mechanisms of action have become the backbone of numerous combination treatments in the newly diagnosed and relapsed/refractory settings. Although IMiD agent–based combination regimens provide improved clinical outcomes for patients with MM, the mechanisms underpinning these combinations are not well understood. In this review we describe the potential mechanisms of synergy leading to the enhanced activity observed when IMiD agents and other drug classes are used in combination through interrogation of the current knowledge surrounding their mechanism of actions.