Novel Treatment Strategies in the Management of Waldenström Macroglobulinemia

Purpose of Review: Recent advances the genomic profiling of patients with Waldenström macroglobulinemia (WM) have led to the identification of novel therapeutic targets in these patients. In this review, we cover the current standard of care and the recently evaluated novel approaches with high potential to be incorporated in the therapeutic armamentarium against WM. Recent Findings: The MYD88^L265P mutation is the most common genomic abnormality in WM, and is encountered in 80–95% of patients, making it an important target for drug development. The success of the first-generation Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has generated tremendous interest in the study of more selective and potent BTK inhibitors. Additionally, the identification of CXCR4^WHIM mutations in up to approximately 40% of patients with WM has fueled research regarding their implication on systemic therapy in WM. Summary: In a rapidly advancing field of targeted therapies, the treatment options for patients with WM are expanding as researchers continue to uncover and harness the survival pathways active in this hematologic malignancy.