BTK Inhibitors in the Frontline Management of Waldenström Macroglobulinemia

The discovery of MYD88 (L265P) mutation led to investigating BTK inhibitors in Waldenström macroglobulinemia (WM). Ibrutinib, the first-in-class agent, was approved based on a phase II trial in relapsed/refractory patients. In the phase III iNNOVATE study, the combination of rituximab and ibrutinib was compared with rituximab and placebo in treatment-naïve and relapsed/refractory patients. Second-generation BTK inhibitor, zanubrutinib, was compared with Ibrutinib in MYD88-mutated WM patients in the phase III ASPEN trial, whereas acalabrutinib was investigated in a phase II trial. Here, we discuss the role of BTK inhibitors in treatment-naïve patients with WM based on currently available evidence.