Novel Treatment Options for Waldenström Macroglobulinemia

Abstract

Waldenström’s macroglobulinemia first described by Jan Waldenström in 1944 is a lymphoplasmacytic lymphoma characterized by the presence of an immunoglobulin M (IgM) monoclonal gammopathy in the blood and monoclonal small lymphocytes and lymphoplasmacytoid cells in the bone marrow. WM is a rare and indolent disease but remains incurable. In this review we discuss the pathogenesis of Waldenström macroglobulinemia and focus on novel treatment options that target pathways deregulated in this disease. Recent studies have helped us identify specific genetic mutations that are commonly seen in WM and may prove to be important therapeutic targets in the future. We discuss the role of epigenetics and the changes in the bone marrow microenvironment that are important in the pathogenesis of WM. The commonly used drugs are discussed with a focus on novel agents that are currently being used as single agents or in combinations to treat WM. We finally focus on some agents that have shown preclinical efficacy and may be available in the near future.

BDR in newly diagnosed patients with WM: final analysis of a phase 2 study after a minimum follow-up of 6 years

“…1,2 Median survival is ;8 to 10 years, and the disease varies from one with indolent course to a disease that needs rapid control. [3][4][5] WM cells express CD20 surface antigen; therefore, rituximab has become a key treatment component; however, it is associated with a modest response rate of ;30% and long time to response. [6][7][8] Thus, it is recommended that primary treatment should consist of rituximab-based combinations, to increase response rates and shorten time to response.…”

Microarray-Based Gene Expression Analysis Identifies Potential Diagnostic and Prognostic Biomarkers for Waldenström Macroglobulinemia

“…WM is a rare low-grade lymphoproliferative disorder characterized by the presence of monoclonal IgM paraprotein in the serum and lymphoplasmacytic infiltration of the bone marrow [15,16]. Chng et al [17] reported a relatively homogeneous expression profile among the WM cases, indicating that WM was more similar to chronic lymphocytic leukemia than multiple myeloma.…”

Waldenström Macroglobulinemia: Mechanisms of Disease Progression and Current Therapies

“…Mesenchymal stem cells (MSCs) serve as the progenitor for most bone marrow stromal cell populations, including osteoblasts, chondrocytes, fibroblasts, endothelial cells, and myocytes [ 18 ]. In WM, BMSCs have been shown to regulate the proliferation of tumor cells while contributing to increased drug therapy resistance [ 19 ].…”