Proteasome inhibitors in the treatment of multiple myeloma

Proteasome inhibition has been shown to be an effective strategy for the treatment of multiple myeloma, as demonstrated by the clinical activity of the first-in-class agent bortezomib. Recently, the second-generation proteasome inhibitor carfilzomib has been approved in the USA in the relapsed and refractory setting, and several other investigational agents are in clinical development, including MLN9708, marizomib, oprozomib and delanzomib. Here, the authors provide a comprehensive review of the key role of proteasome inhibitors in the myeloma treatment pathway, and highlight the similarities and differences in pharmacology, routes of administration, and efficacy and safety profiles between bortezomib, carfilzomib and investigational agents. The authors also evaluate the potential for further improving myeloma treatment through the ongoing development of novel proteasome inhibitors.