Based on the observation, that ibrutinib single agent has less activities in CXCR4 mutated patients and in patients with non-mutated MYD88 and CXCR4, a large international prospective study performed on behalf of the European Consortium for Waldenström’s Macroglobulinemia (ECWM) was initiated, randomizing 150 patients with treatment naive or pretreated WM between ibrutinib plus rituximab or placebo plus rituximab. This evidence concerns the gene CXCR4 and macroglobulinemia.