The investigational proteasome inhibitor ixazomib for the treatment of multiple myeloma. (April 2015)

• Record Type: Journal Article
• Authors: Richardson, Paul G; Moreau, Philippe; Laubach, Jacob P; Gupta, Neeraj; Hui, Ai-Min; Anderson, Kenneth C; San Miguel, Jesús F; Kumar, Shaji
• Is Part Of: Future oncology. Volume 11:Number 8(2015)
• Page Start: 1153
• Page End: 1168
• Publication Date: 2015-04
• Subjects: continuous therapy -- induction -- multiple myeloma -- newly diagnosed -- oral administration -- proteasome inhibition -- refractory -- relapsed; Oncology -- Periodicals; 616.99405
• DOI: 10.2217/fon.15.9
• Languages: English
• ISSNs: 1479-6694

Abstract

ABSTRACT : Ixazomib is an investigational, reversible 20S proteasome inhibitor. It is the first oral proteasome inhibitor under clinical investigation in multiple myeloma (MM). Under physiological conditions, the stable citrate ester drug substance, ixazomib citrate (MLN9708), rapidly hydrolyzes to the biologically active boronic acid, ixazomib (MLN2238). Preclinical studies have demonstrated antitumor activity in MM cell lines and xenograft models. In Phase I/II clinical studies ixazomib has had generally manageable toxicities, with limited peripheral neuropathy observed to date. Preliminary data from these studies indicate ixazomib is active as a single agent in relapsed/refractory MM and as part of combination regimens in newly diagnosed patients. Phase III studies in combination with lenalidomide–dexamethasone are ongoing.