Safety of proteasome inhibitors for treatment of multiple myeloma

Abstract

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.

In Vitro Assessment of Antitumor Potential and Combination Effect of Classical and Molecular-targeted Anticancer Drugs

“…Bmib is mainly used as a therapeutic agent for refractory multiple myeloma in hematology clinic, due to its potent anti-tumor activity and yet-unknown biological function (16). It has been reported that Bmib caused the high incidence of neutropenia and stomatitis (17), peripheral neuropathy (18) and epidermal necrolysis (19). We also found potent cytotoxicity of Bmib against OSCC cell lines as well as normal oral cells, especially oral keratinocytes.…”

<p>RING Finger Protein 38 Mediates LIM Domain Binding 1 Degradation and Regulates Cell Growth in Colorectal Cancer</p>

“…In recent years, with the successful application of proteasome inhibitor bortezomib in the treatment of multiple myeloma, ubiquitination of proteins has entered a new research level. 16 A series of anti-tumor drugs targeting ubiquitination-related enzymes, including E1, E2, E3 and DUBs, have been developed for cancer treatment. 17 For example, PYR-41, an inhibitor of E1, was used in anticancer research.…”

Living with relapsed myeloma: Symptoms and self‐care strategies

“…Difficult symptoms such as PN can result in significant disability and pain (Colson, ). It is crucial that there is frequent assessment of neuropathic symptoms and the early detection of neuropathic pain before it gets progressively worse (Colson, ; Schlafer, Shah, Panjic, & Lonial, ).…”