ABSTRACT
Despite major advances in the treatment of newly diagnosed multiple myeloma (MM), the vast majority of patients relapse after induction therapy and therefore require further treatment. Historically, the mainstay of therapy for patients with relapsed MM has been high dose dexamethasone or dexamethasone-based regimens, but these have failed to impact survival. Fortunately, in the past eight years there have been significant advances in the treatment of relapsed and relapsed, refractory MM through the development, and U.S. Food and Drug Administration (FDA) approval, of two major new classes of therapeutic agents; lenalidomide and thalidomide as immunomodulatory drugs, and bortezomib as a first-inclass proteasome inhibitor (1,2). These drugs represent a new paradigm of antitumor agent which not only target the MM cell directly, but also have significant activity against key tumor cell interactions with the bone marrow microenvironment (3). Both lenalidomide and bortezomib have been shown to be superior to high dexamethasone in the relapsed setting and confer significant survival advantage to patients with relapsed MM (4,5). Preclinical and clinical studies to date have also shown that the combination of these agents, in particular bortezomib, with targeted therapy and conventional chemotherapy enhances their anti-MM activity (6). Furthermore, there continues to be progress in the development of
additional novel immunomodulatory drugs and second generation proteasome inhibitors, with potentially enhanced activity. In this chapter, we will review the role of these agents, both as monotherapy and as combinations in the treatment of relapsed MM, as well as other emerging novel agents that are currently in development.
