Steven Treon, MD, PhD, Dana-Farber Cancer Institute, Boston, MA, discusses the optimal sequencing of therapies in Waldenström’s macroglobulinemia (WM) and the importance of genomics in determining the most appropriate therapy for patients. Dr Treon first discusses treatment options for patients with MYD88 mutation, and further explains the safety and efficacy of ibrutinib therapy in these patients. Dr Treon then discusses options for patients with CXCR4 mutation, as well as the promise of novel BTK inhibitors including zanubrutinib. This interview took place at the 8th World Congress on Controversies in Multiple Myeloma (COMy) 2022, held in Paris, France.