Safety of proteasome inhibitors for treatment of multiple myeloma

Introduction: Proteasome inhibitors (PIs) have revolutionized the treatment of multiple myeloma and are a backbone of therapy. Bortezomib, the first PI approved, has shown efficacy in both front-line and relapsed/refractory settings however the development of resistance and side effects such as peripheral neuropathy can limit its use. The second generation PIs carfilzomib and ixazomib, both approved in relapsed/refractory cases, may help to overcome resistance mechanisms and increase tolerability. While bortezomib is approved to be administered intravenously (IV) or subcutaneously (SC) and carfilzomib IV, ixazomib is the first and only approved PI that is orally bioavailable. Areas covered: This review focuses on the safety data from clinical trials for the three approved PIs and how to manage adverse effects. A summary of efficacy data from select clinical trials is also included. Expert commentary: Targeting the proteasome/ubiquitin system is a validated and important part of current anti-myeloma therapy. The availability of an oral proteasome inhibitor without significant neuropathy as a side effect offers patients an important step forward over their treatment.