Relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib

psed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib Review (888) Total Article Views Authors: Nooka A, Gleason C, Casbourne D, Lonial S Published Date January 2013 Volume 2013:7 Pages 13 - 32 DOI: http://dx.doi.org/10.2147/BTT.S24580 Received: 03 April 2012 Accepted: 08 June 2012 Published: 30 January 2013 Ajay Nooka, Charise Gleason, Daniela Casbourne, Sagar Lonial Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta GA, USA Abstract: Proteasomal inhibition revolutionized myeloma therapies in this decade of novel agents. The only US Food and Drug Administration approved proteasome inhibitor so far, bortezomib effectively targets the constitutive proteasome subunit 5 of the 26S proteasome. Bortezomib induces high and quality response rates that are durable. However, myeloma cells acquire resistance to bortezomib through various mechanisms. Further, grade 3/4 peripheral neuropathy is seen in up to a quarter of patients treated with bortezomib. While the recent change in the mode of administration via the subcutaneous route is associated with a lower incidence of grade 3/4 peripheral neuropathy, it remains a major concern. The second generation proteasome inhibitors are promising, with increased preclinical efficacy and a better administration schedule. The current review spotlights the second generation proteasome inhibitors with special focus on the safety and efficacy of carfilzomib, an epoxyketone with lesser peripheral neuropathy, which exhibits irreversible proteasome inhibition. In this article, we review the pharmacology and preclinical and clinical efficacy and safety of carfilzomib alone and in combination with other chemotherapeutic agents in the various lymphoid neoplasms and multiple myeloma as well as ongoing clinical trials.