Subtype Report: Waldenström's Macroglobulinemia
Patients with WM show a variable course of disease progression and it is therefore critical to identify the need for treatment. There are multiple options for treatment; however, the regimen requires thoughtful selection keeping in mind the patient’s age, comorbidities, IgM levels, and genetic mutations.
Within the course of a few years, the understanding of WM has been substantially increased. One of the greatest discoveries was the prevalence of MYD88 somatic mutations in patients with WM. Further studies have shown that this mutation in 80% of patients with IgM MGUS significantly increases their chances of early diagnosis. It has also helped with the difficulties faced by haematologists in differentiating between marginal zone lymphoma, multiple myeloma, and chronic lymphocytic leukemia due to overlapping characteristics. These breakthroughs can be exploited therapeutically.
Downstream targets of MYD88 such as IRAK1, IRAK4, BTK, and TAK1 can all prove to be important markers for future drug targets. BTK is targeted by ibrutinib which translates into the efficacy of the drug with patients shown to have MYD88 L265P. New therapies provide an opportunity to drastically affect patient outcomes positively and improve overall survival, rather than relying on inherited treatments from other lymphomas which often lead to comorbidities such as secondary cancers and complications from IgM flare.
Many new agents have emerged in the last couple of years that improve responses and reduce long term toxicities. However, better understanding of the biology can further improve outcomes. Whole genome sequencing studies are helping to identify specific mutations in subgroups of patients with WM.
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