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The Direction of Modern Therapies in Waldenström Macroglobulinaemia
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The Direction of Modern Therapies in Waldenström Macroglobulinaemia
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Journal Article
The Direction of Modern Therapies in Waldenström Macroglobulinaemia
2025
Overview
Waldenström macroglobulinaemia (WM) is a rare lymphoplasmacytic disease that is hallmarked by B‐cell infiltration of the bone marrow, an overexpression of IgM class antibodies and an activating mutation of MYD88 (L265P). The therapeutic options for WM patients include a combination of Rituximab (anti‐CD20 monoclonal antibody) and chemotherapy, with newer treatments like proteasomal inhibitors and Bruton's Tyrosine Kinase (BTK) inhibitors showing high levels of success both as monotherapy and in combinations. To date, WM remains incurable. Understanding the basic physiology of WM and creating new and improved pre‐clinical models which better reflect the true physiology of WM will allow for the identification of novel therapeutic vulnerabilities and the ability to test these next generation therapies, both in a tumour intrinsic and extrinsic manner. In this review, we aim to provide a comprehensive summary of WM, focusing on the genetic mutations and signalling pathways driving disease progression. In addition, we highlight the current therapeutics and emerging clinical trials to provide novel insights to drive deep and durable responses.
Publisher
John Wiley & Sons, Inc
Subject
Agammaglobulinaemia Tyrosine Kinase - antagonists & inhibitors
/ Analysis
/ Animals
/ B cells
/ Cancer
/ Disease
/ Humans
/ Hypoxia
/ Kinases
/ Mutation
/ Myeloid Differentiation Factor 88 - genetics
/ Proteins
/ Signal Transduction - drug effects
/ Tyrosine
/ Waldenstrom Macroglobulinemia - drug therapy
/ Waldenstrom Macroglobulinemia - genetics
/ Waldenstrom Macroglobulinemia - metabolism
/ Waldenstrom Macroglobulinemia - pathology
