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Waldenström Macroglobulinemia (WM) is an incurable hematologic malignancy characterized by lymphoplasmacytic infiltration of the bone marrow and the presence of monoclonal immunoglobulin (IgM). Although a portion of WM patients may experience a relatively indolent course, patients may experience IgM-related morbidity and/or disease-related mortality. This underscores the need for novel approaches to improve response and survival rates. Significant progress had been made in our understanding of the genomics and biology of WM. The discovery of the highly recurrent somatic mutations in the MYD88 gene detected in 90–95% and the CXCR4 gene detected in 30–40% of WM patients has provided an opportunity to develop novel targeted approaches. Mutational status has important implications in predicting response to therapies such as BTK inhibitors. Treatment of WM should be guided by many factors including performance status, comorbidities, goals of therapy, and toxicities. In this review, we describe how current genomics may be utilized to optimize WM treatment selection. As the therapeutic landscape of WM continues to expand with more targeted approaches, the genomics in WM will likely play a greater role in individualizing treatment. [ABSTRACT FROM AUTHOR]

The article presents a case study of a patient with MYD88-mutated IgG -lambda lymphoplasmacytic lymphoma (LPL) who underwent salvage therapy with ibrutinib drug . Topics include the patient diagnosed with IgG LPL in August 2000, when experiencing fatigue and night sweats, and the patient stated to have been presented with worsening right-sided preauricular lymphadenopathy.

Cases of non-IgM lymphoplasmacytic lymphoma (LPL) are rare. We performed a case–control study comparing features and outcomes of 31 non-IgM LPL cases and 93 Waldenström macroglobulinemia (WM) controls matched by age, sex, and year of diagnosis. Odds of MYD88 mutations were lower (odds ratio (OR) 0.22, p =.05), and median time to treatment was shorter in cases than in controls (4 vs. 32 months; p <.001). Odds of extramedullary disease were higher (OR 4.20, p =.01), while odds of neuropathy (OR 0.22, p =.25), and hyperviscosity (OR 0.26, p =.26) were lower in cases than in controls. Odds of using chemoimmunotherapy were higher (OR 2.62, p =.11) while odds of using proteasome inhibitors (OR 0.35, p =.15) and BTK inhibitors (OR 0.17, p =.21) were lower in cases than in controls. There were no differences in response and overall survival (OS) between cases and controls. Despite clinicopathological differences, response, and survival outcomes are similar between non-IgM LPL cases and WM controls. [ABSTRACT FROM AUTHOR]

The article presents research on the use of hematologic drug Idelalisib in treating patients with Waldenström macroglobulinemia (WM). Topics discussed include an overview of Waldenström macroglobulinemia, the activation of phosphatidylinositol-3-kinase (PI3K) pathway, and the benefit of idelalisib to patients..

Histone deacetylases (HDACs) are aberrantly expressed, and inhibitors of HDACs induce apoptosis in lymphoplasmacytic cells (LPCs) in Waldenström macroglobulinemia (WM). The molecular profile by which these agents induce apoptosis in WM LPCs remains to be delineated. We examined the activity of the histone deacetylase inhibitor, vorinostat, and dissected its pro-apoptotic pathways in WM LPCs. Vorinostat induced apoptosis in WM cells through activating specific caspases at varying times. Inhibitors of apoptosis (IAPs) were down-regulated after vorinostat treatment. Cellular stress induced in vorinostat-treated WM cells was reflected by changes in the mitogen activated protein kinase (MAPK) pathways. Activated phospho-p38 MAPK was up-regulated at 12 h, while phospho-extracellular signal-regulated kinase (Erk) abruptly decreased at 24 h. Bortezomib did not augment vorinostat induced primary WM cell killing as reported in other B-cell disorders. These studies support that stress induced apoptosis in vorinostat-treated WM LPCs is mediated through disrupting the activity of the Erk and p38 MAPK pathways. [ABSTRACT FROM AUTHOR]

The serum IgM level has been utilised as a marker of tumor progression and to assess response to therapy in patients with Waldenstrom macroglobulinemia (WM). However, there are many limitations to the IgM protein level. The objective of this study was to evaluate the association of known tumor burden markers and prognostic factors with serum free light chain (sFLC) in 98 patients with WM. We demonstrated that sFLC measurement accurately differentiated IgM-MGUS compared with WM reflecting a measurement of tumor burden. In univariate and multivariate analysis, median sFLC at the cut-off at 60 mg/L was higher for WM patients with low hemoglobin and high β2M, when we applied the WM-IPSS cut-offs, but showed no association with IgM level. This study demonstrates that sFLC is a new marker in WM disease. Further analysis is required to prospectively study the role of sFLC in monitoring response to therapy and as a prognostic marker in WM patients. [ABSTRACT FROM AUTHOR]