Genomics and the Optimal Management of Waldenström Macroglobulinemia

Steven Treon, MD, PhD


July 16, 2020

Waldenström macroglobulinemia is an indolent B-cell lymphoproliferative disorder characterized by excess secretions of the IgM protein. Dr Steven Treon discusses the role of MYD88 and CXCR4 gene mutations, and how they affect current and future treatment options for patients with Waldenström macroglobulinemia.

Patients may present with anemia (70%-80%), fatigue, hyperviscosity syndrome, IgM-related neuropathy, and extramedullary disease. Approximately 95% of Waldenström macroglobulinemia patients have the MYD88 mutation, which is used not only as a diagnostic marker but also as a guideline for treatment decisions.

Patients with the MYD88 mutation respond well to Bruton tyrosine kinase (BTK) inhibitors and demonstrate greater overall survival. Those lacking the MYD88 gene benefit from the use of a proteasome inhibitor combined with rituximab or the use of bendamustine plus rituximab.

CXCR4 mutations, which are found in 40% of patients who have the MYD88 mutation, delay the responses of BTK inhibitors, affect the depth of response (very good partial response), and lessen the duration of progression-free survival. Consequently, an accurate genetic characterization of Waldenström macroglobulinemia is essential for the optimal treatment of this disease.

Dr Treon looks forward to the results of clinical trials examining CXCR4 antagonists and BTK inhibitors combined with target mediated signaling, as they could provide promising therapeutic options for this patient type.


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