Clinical potential of carfilzomib in the treatment of relapsed and refractory multiple myeloma

• Type of Material: Article
• Authors: Vikas Gupta, Emory University; Ajay Nooka, Emory University; Sagar Lonial, Emory University; Lawrence Boise, Emory University
• Language: English
• Date: 2013-05-16
• Publisher: Dovepress
• Publication Version: Final Published Version
• Copyright Statement: © 2013 The Author(s).
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): https://doi.org/10.2147/BLCTT.S31867
• Title of Journal or Parent Work: Blood and Lymphatic Cancer: Targets and Therapy
• Volume: 3
• Start Page: 41
• End Page: 51
• Keywords: efficacy; proteasome inhibitor; safety; pharmacology; bortezomib
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Oncology

Abstract

Treatment of refractory and/or relapsed multiple myeloma has been a challenging problem for over 20 years. However, we have made significant progress addressing this disease with the use of bortezomib, the first in class proteasome inhibitor, and the immunomodulatory agents, thalidomide and lenalidomide. Carfilzomib, the second-generation proteasome inhibitor, has also been approved for treatment of relapsed/refractory multiple myeloma. Carfilzomib is a highly selective and potent inhibitor of proteasome chymotrypsin-like activity. Phase I and II clinical trials have reported an acceptable toxicity profile, with manageable thrombocytopenia and anemia being the most common side effects. Peripheral neuropathy, a frequent dose-limiting side effect of bortezomib, was rare. Further, carfilzomib demonstrated encouraging single-agent activity and appeared to be effective even in patients refractory to bortezomib. Based on these promising data, carfilzomib is moving forward into Phase III trials for relapsed multiple myeloma and is also being investigated as front-line combination therapy for patients with newly diagnosed myeloma.