Evaluating ibrutinib in the treatment of symptomatic Waldenstrom’s macroglobulinemia

Abstract

Aristea-Maria Papanota,* Ioannis Ntanasis-Stathopoulos,* Efstathios Kastritis, Meletios A Dimopoulos, Maria GavriatopoulouDepartment of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital, Athens, GreeceCorrespondence: Maria GavriatopoulouDepartment of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital, 80 Vas. Sofias Avenue, Athens 11528, GreeceTel [phone]Fax [phone]Email [email protected]*These authors contributed equally to this workAbstract: 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.Keywords: Waldenstrom’s macroglobulinemia, IgM, ibrutinib, Bruton’s tyrosine kinase

Keywords

• Waldenstrom’s macroglobulinemia
• IgM
• ibrutinib
• Bruton’s tyrosine kinase