Evaluating ibrutinib in the treatment of symptomatic Waldenstrom's macroglobulinemia.

Waldenstrom's macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma with indolent course and prolonged disease course. The first-in-class Bruton's tyrosine kinase inhibitor, ibrutinib, has shown significant activity and a distinct adverse event profile among both newly diagnosed and relapsed/refractory WM patients. Interestingly, clinical responses to ibrutinib have been shown to be dependent on patients' MYD88 and CXCR4 mutational status. The recent outcomes of the Phase III iNNOVATE trial showed that the combination of ibrutinib with rituximab resulted in a significantly prolonged progression-free survival compared with rituximab monotherapy, which provides a novel therapeutic option in the clinical practice especially for the rituximab-refractory WM patients. However, the need for continuous drug administration along with the unique toxicity manifestations may render the patient management challenging. Furthermore, our understanding of the underlying resistant mechanisms to ibrutinib is currently being evolved.