Phase II clinical trials for Waldenstrom's macroglobulinemia

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.