Preclinical models of Waldenström's macroglobulinemia and drug resistance

Newer therapeutic strategies are emerging in Waldenström's Macroglobulinemia (WM), which has traditionally been an orphan disease diagnosis. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor was FDA-approved in 2015 as the first ever drug for the treatment of WM. This being a targeted therapy, has given rise to increased research into novel agents and pathways that can be exploited for clinical benefit in WM. In order to understand the underlying mechanisms of disease behavior as well as to test the benefit of various drugs, appropriate preclinical models are required. Historically there had been a lack of representative preclinical models in WM, but in recent years this has dramatically changed. This review highlights the currently available preclinical models and data regarding drug resistance pathways in WM. Knowledge from these will certainly help in paving the future course of treatment in this rare disorder which is indolent and yet, so far incurable.