Molecular Profiling of Waldenstrom Macroglobulinemia
The World Health Organization (WHO) defines Waldenstrom Macroglobulinemia (WM) as a low-grade non-Hodgkin lymphoma characterized by infiltration of bone marrow with lymphoplasmacytic cells and the presence of monoclonal IgM immunoglobulin protein in the serum (Campo et al. 2011). WM accounts for 1–2% of hematologic malignancies and >95% of all lymphoplasmacytic lymphoma cases (Kapoor et al. 2015). It is twice as prevalent in males and white populations, compared to females and African Americans, respectively (Wang et al. 2012). The median age of diagnosis is between 63–73 years, and the median overall survival ranges from 5–11 years (Castillo et al. 2014; Garcia-Sanz et al. 2001; Morel et al. 2000; Morel et al. 2009; Nelson et al. 2013). The main causes of mortality are disease progression, complications resulting from treatment, and transformation to a higher grade lymphoma.
Mutations in the MYD88 gene are widely prevalent in WM and are seen in 90–95% of the patients, with L265P being the predominant mutation (Growkova et al. 2017; Treon et al. 2011). The second most commonly mutated gene is CXCR4, which is mutated in about 40% of the patient population (Jimenez et al. 2013; Mori et al. 2013; Varettoni et al. 2013). Ibrutinib was the first drug approved by the FDA for the treatment of WM (FDA 2017).
WM is currently incurable; treatment efforts focus on symptom management and preventing organ damage. About 25% of WM patients are asymptomatic (Alexanian et al. 2003; Garcia-Sanz et al. 2001) and are followed by surveillance. There are several treatment regimens available for symptomatic patients—those exhibiting hyperviscosity, anemia, lymphadenopathy, hepatomegaly, splenomegaly among other clinical features.
Last Updated: February 26, 2018