Phase II clinical trials for Waldenstrom’s macroglobulinemia

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords:

• bendamustine
• Bruton tyrosine kinase inhibitors
• HDAC inhibitors
• immunomodulators
• mammalian target of rapamycin inhibitors
• MYD88 (L265P)
• PI3K/AKT/PKC inhibitors
• proteasome inhibitors
• Waldenstrom’s macroglobulinemia

Declaration of interest

MA Gertz has received honoraria from Onyx, Millennium, Celgene, Med Learning Group, Novartis and Research to Practice. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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