The role of ibrutinib in Waldenström macroglobulinemia

Introduction: Waldenström macroglobulinemia (WM) is an uncommon incurable B-cell lymphoma characterized by the presence lymphoplasmacytic cells in the bone marrow. The recurrent mutation in the MYD88 gene and the deeper understanding of the biology of the MYD88 signaling pathway provided the opportunity to develop targeted drugs.Areas covered: Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor, which has been recently approved by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for patients with symptomatic Waldenström macroglobulinemia (WM). In this review we aim to present the role of BTK in WM pathophysiology and highlight the role of ibrutinib in the treatment of the disease.Expert opinion: Ibrutinib is an orally administered agent proven to be safe and highly effective which has changed the treatment landscape of the disease. Approximately 90% of the patients will eventually respond to ibrutinib, the responses are deep and durable while only a few discontinue treatment due to treatment related toxicity. Ibrutinib also seems to be extremely effective even in heavily pretreated and rituximab refractory patients in which almost 75% will respond to this treatment regimen. Several studies are ongoing in order to investigate the most appropriate combinations and timepoints of the disease in which ibrutinib should be administered in order to improve response, survival rates and quality of life.