Phase II clinical trials for Waldenstrom's macroglobulinemia. (May 2015)

• Record Type: Journal Article
• Authors: Chakraborty, Rajshekhar; Ansell, Stephen A; Kapoor, Prashant; Gertz, Morie A
• Is Part Of: Expert opinion on orphan drugs. Volume 3:Number 5(2015:May)
• Page Start: 537
• Page End: 547
• Publication Date: 2015-05
• Subjects: Orphan drugs -- Periodicals; Rare diseases -- Periodicals; Chemotherapy -- Periodicals; 615.1
• DOI: 10.1517/21678707.2015.1025749
• Languages: English
• ISSNs: 2167-8707

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Introduction:</italic> </bold> Waldenstrom's macroglobulinemia (WM) is an indolent lymphoma, characterized by infiltration of bone marrow by lymphoplasmacytic cells producing monoclonal immunoglobulin M protein. Many patients with WM may be observed, with chemotherapy reserved for symptomatic disease. Five-year survival rates vary from 36% in high-risk to 87% in low-risk patients. Studies in WM have shown improving survival over time. Recent insights into pathogenesis have revealed new targets for therapy, including mammalian target of rapamycin (mTOR) pathway and PI3K/Akt/PKC pathway among others. Whole genome sequencing has identified novel activating somatic mutations in WM, including MYD88 and CXCR4, which could serve as potential targets for management.</p> <p> <bold> <italic>Areas covered:</italic> </bold> This paper summarizes Phase II trials incorporating novel therapeutic agents, including proteasome inhibitors, immunomodulators, inhibitors of mTOR and PI3K/Akt/PKC pathways, Bruton tyrosine kinase inhibitors, bendamustine and HDAC inhibitors. A comprehensive literature search was undertaken in PubMed, Ovid Medline, Ovid Embase and Web of Science databases and all relevant studies were included.</p> <p> <bold> <italic>Expert opinion:</italic> </bold> Rituximab is considered as a first-line agent in the management of WM, with rituximab–cyclophosphamide–dexamethasone and rituximab–bendamustine being preferred regimens. Second-line regimens include proteasome inhibitors and purine analogs.</p> </abstract>