BTK inhibition has changed the treatment landscape of Waldenström’s macroglobulinemia (WM). Steven Treon, MD, PhD, Dana-Farber Cancer Institute, Boston, discusses new BTK inhibitors under investigation that are emerging as promising therapeutics. Single agent acalabrutinib has recently been evaluated in a Phase II study (NCT02180724) of patients with WM, demonstrating impressive response rates and progression-free survival data. Additionally, zanubrutinib, a second-generation BTK inhibitor, has been compared to ibrutinib in the ASPEN trial (NCT03053440). Zanubrutinib demonstrated significant efficacy in patients independent of MYD88 mutation status and showed less cardiovascular adverse events than ibrutinib. While the superiority of zanubrutinib with regards to depth of response was not demonstrated, the data suggests longer follow-up may reveal its clinical potential. This interview took place during the 7th World Congress on Controversies in Multiple Myeloma (COMy), 2021.