A Head-To-Head Phase III Study Comparing Zanubrutinib Versus Ibrutinib in Patients with Waldenström Macroglobulinemia

Abstract

Waldenström macroglobulinemia (WM), an incurable B-cell malignancy, is sensitive to Bruton tyrosine kinase (BTK) inhibition with ibrutinib, a first-generation BTK inhibitor. Off-target effects of ibrutinib against TEC- and EGFR-family kinases are implicated in some adverse events. Patients with CXCR4^WHIM and MYD88^L265P mutations or who are MYD88^WT have less sensitivity to ibrutinib than those with MYD88^L265P and CXCR4^WT disease. Zanubrutinib, a next-generation BTK inhibitor with potent preclinical activity in WM and minimal off-target effects, showed sustained BTK occupancy in peripheral blood mononuclear cells from patients with B-cell malignancies and promising responses in advanced WM. Described here is a head-to-head Phase III study comparing efficacy and safety of zanubrutinib and ibrutinib in WM patients. Effect of MYD88 and CXCR4 mutation status will be assessed.