Steven Treon, MD, PhD, Dana-Farber Cancer Institute, Boston, MA, discusses the use of BTK inhibitors in the management of Waldenström’s macroglobulinemia (WM). BTK inhibitors can be useful in the management of WM. For example, ibrutinib and zanubrutinib can bind to HCK and help mitigate aberrant MYD88 signaling in WM, whereas some BTK binding can exacerbate side effects, for example, BTK inhibitor binding to IGFR and ITK. Dr Treon expresses the need to consider each BTK inhibitor drug individually rather than as an umbrella class of drug due to safety variability. Dr Treon comments on the ASPEN trial (NCT03053440) comparing the safety and efficacy of zanubrutinib and ibrutinib in WM and on how results from this trial suggested a difference in the side effect profile of the respective drugs. It is important for clinicians to consider the individual predispositions of their patients to the side effect profiles of these drugs to ensure the best treatment outcomes for patients with WM. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.