Lymphoplasmacytic lymphoma (LPL) is a form of B-cell neoplasm in which the malignant cells have characteristics of both lymphocytes and plasma cells. Waldenström macroglobulinemia (WM) is another frequently used name for this condition. Typically, these cells produce excess amounts of IgM, termed monoclonal gammopathy. In some cases, IgG is also present. This results in thick, hyperviscous blood which can lead to neurological and visual symptoms. Excess bleeding may also occur due to the interference of IgM with normal clotting factors (Kaseb et al., 2022).
Diagnosis of LPL/WM is supported by demonstration of bone marrow infiltration by small lymphocytes which show plasmacytoid or plasma cell differentiation as well as characteristic immunophenotyping studies (CD19+, CD20+, IgM+). However, diagnosis can be challenging as bone marrow can exhibit similar features as other B-cell neoplasms, including marginal zone lymphoma, follicular lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, and mantle cell lymphoma (Kaseb et al., 2022). The MYD88 L265P pathogenic variant is present in more than 90% of LPL/WM cases (Yu et al., 2018). Allele-specific PCR testing of bone marrow for MYD88 (L265P) is recommended by the National Comprehensive Cancer Network® (NCCN®) as an essential test in the diagnostic workup of this condition. The presence of this pathogenic variant is useful in differentiating LPL from non-IgM LPL and other B-cell malignancies. Accurate diagnosis allows for appropriate clinical management (NCCN v.1.2023).
Most patients with LPL/WM are asymptomatic, and may be candidates for watchful waiting due to the indolent nature of this condition. The primary treatment for patients with symptoms of hyperviscous blood is plasmapheresis. Depending on response, chemotherapies may be warranted (Gertz, 2018). Common somatic pathogenic variants in the CXCR4 gene have been reported in up to 40% of patients with LPL/WM, and studies have shown an association with resistance to ibrutinib. Given the potential impact on treatment decisions, NCCN recommends CXCR4 pathogenic variant testing for patients with LPL/WM who are being considered for treatment with Bruton’s tyrosine kinase (BTK) inhibitors (NCCN v.1.2023).
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma V.1.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed [January 20, 2023]. To view the most recent and complete version of the guideline, go online to NCCN.org.
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