How we use Genomics and BTK-Inhibitors in the Treatment of Waldenstrom Macroglobulinemia

Mutations in MYD88 (95-97%) and CXCR4 (30-40%) are common in Waldenstrom macroglobulinemia (WM). TP53 is also altered in 20-30% of WM patients, particularly those previously treated. Mutated MYD88 upregulates and activates HCK that drives BTK pro-survival signaling. Both nonsense and frameshift CXCR4 mutations occur in WM. Nonsense variants such as CXCR4S338X show greater resistance to BTK-inhibitors. Covalent BTK-inhibitors (cBTK-i) produce major responses in 70-80% of WM patients. MYD88 …