Current and emerging treatment perspectives for adults with Waldenström macroglobulinemia

Expert Rev Anticancer Ther. 2025 May;25(5):485-497. doi: 10.1080/14737140.2025.2488312. Epub 2025 Apr 3.

Abstract

Introduction: Waldenström Macroglobulinemia (WM) is distinguished from other indolent lymphomas by its unique molecular landscape and clinical behavior. With the emergence of new therapeutic options and improved survival rates, it has become increasingly important to balance the goal of prolonging survival with minimizing treatment-related toxicities.

Areas covered: This review focuses on the current therapeutic strategies for WM, emphasizing the clinical effectiveness of various agents and treatment groups and their associated toxicity profiles. Additionally, we discuss emerging therapies and combinations, which have shown encouraging preliminary results.

Expert opinion: WM remains an incurable disease, yet its indolent nature and the growing array of therapeutic options have significantly improved outcomes in first- and subsequent-line settings. Chemoimmunotherapy and BTK inhibitors have demonstrated high efficacy and durable responses, with the latter offering a stem-cell-sparing approach. However, unlike in CLL or multiple myeloma, evidence supporting the superiority of targeted agents over chemoimmunotherapy is not available. Consequently, treatment decisions depend on patient characteristics and shared decision-making to carefully balance risks, select appropriate regimens, and encourage clinical trial participation to advance in understanding this rare disease.

Keywords: Chemotherapy; Waldenström macroglobulinemia; investigational therapies; targeted therapy; treatment response.

Publication types

  • Review

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Clinical Decision-Making
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology
  • Survival Rate
  • Waldenstrom Macroglobulinemia* / drug therapy
  • Waldenstrom Macroglobulinemia* / pathology
  • Waldenstrom Macroglobulinemia* / therapy

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors