Current Phase II investigational proteasome inhibitors for the treatment of multiple myeloma

Introduction: The introduction and exploration of novel agents has significantly improved patient outcome in the treatment of multiple myeloma (MM). One such compound, bortezomib, was the first proteasome inhibitor (PI) to be approved as a MM therapeutic. The efficacy and safety data provided by bortezomib usage has provided the basis for the development of a second generation of PIs. Areas covered: This review focuses on PIs that are currently under evaluation in Phase II clinical trials for the treatment of MM. Furthermore, the article summarizes the currently understood mechanisms of action and the available clinical data for its use in MM. Expert opinion: Second generation PIs have demonstrated promising activity in patients with advanced-stage myeloma, including those refractory to bortezomib. It should be noted, however, that their efficacy in upfront settings is currently under investigation. Future PI development should include schedule optimization and the investigation of PIs potential synergistic activity with other anti-myeloma agents.