The start of a new wave: Developments in proteasome inhibition in multiple myeloma. (2nd May 2018)

• Record Type: Journal Article
• Authors: Yong, Kwee; Gonzalez‐McQuire, Sebastian; Szabo, Zsolt; Schoen, Paul; Hajek, Roman
• Is Part Of: European journal of haematology. Volume 101:Number 2(2018)
• Page Start: 220
• Page End: 236
• Publication Date: 2018-05-02
• Subjects: bortezomib -- carfilzomib -- multiple myeloma -- proteasome -- proteasome inhibitor; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; Blood -- Periodicals; 616.15005
• DOI: 10.1111/ejh.13071
• Languages: English
• ISSNs: 0902-4441

Abstract

Abstract: Multiple myeloma (MM) accounts for 10% of hematological cancers. Stem cell transplantation remains the cornerstone of first‐line treatment for eligible patients, but historically, pharmaceutical treatment options for MM have been limited. The proteasome was identified as a target for MM therapy in the early 2000s and, in 2004, the boronic acid proteasome inhibitor bortezomib gained European approval. Bortezomib now plays a major role in MM treatment, but the duration of its use can be limited by toxicities such as peripheral neuropathy and the development of resistance. A new generation of proteasome inhibitors has since entered the treatment landscape: carfilzomib, an epoxyketone‐based agent with a distinct mode of action, high clinical efficacy, and lower levels of peripheral neuropathy compared with bortezomib, received approval in 2015 for use in patients with relapsed and/or refractory MM (RRMM). Ixazomib, a second‐generation, orally administered, boronic acid proteasome inhibitor, has also been approved for use in patients with RRMM. In just over a decade, proteasome inhibitor‐based regimens have become an integral component of MM treatment; with more proteasome inhibitors in development, this remains a vibrant research area with potential to improve the lives of patients with MM in the years to come.