Current approach to Waldenström Macroglobulinemia.

Area of Science:

• Hematology
• Oncology
• Clinical Research

Background:

• Waldenström Macroglobulinemia (WM) is a rare IgM lymphoplasmacytic lymphoma with variable clinical behavior.
• Limited high-quality evidence from Phase 3 trials complicates treatment decisions despite new therapies.
• MYD88 and CXCR4 mutation status influences treatment selection for WM patients.

Purpose of the Study:

• To review current literature on Waldenström Macroglobulinemia diagnosis, prognosis, and treatment.
• To discuss therapeutic strategies considering patient-specific genetic markers.
• To compare fixed-duration chemo-immunotherapy versus indefinite Bruton's tyrosine kinase (BTK) inhibitor regimens.

Main Methods:

• Comprehensive literature review of WM diagnosis, prognosis, and treatment.
• Analysis of therapeutic options including bendamustine-rituximab (BR) and BTK inhibitors.
• Evaluation of treatment efficacy based on MYD88 and CXCR4 mutation status.

Main Results:

• MYD88 L265P and CXCR4 mutation status guides BTK inhibitor therapy decisions.
• Bendamustine-rituximab (BR) is preferred for MYD88 WT WM, while BTK inhibitors are effective for MYD88 L265P WM.
• Zanubrutinib shows activity in MYD88 WT WM, offering an alternative to chemo-immunotherapy.

Conclusions:

• Optimal treatment selection for WM requires consideration of genetic mutations (MYD88, CXCR4).
• Both BR and BTK inhibitor regimens are effective and well-tolerated, particularly for MYD88 L265P patients.
• Further comparative data is needed to definitively guide treatment choices between different regimens.