In this video, Jorge Castillo, MD, of the Dana-Farber Cancer Institute, Boston, MA, discusses the use of novel agents in the management of Waldenström’s macroglobulinemia. Dr Castillo focuses on the use of Bruton’s tyrosine kinase (BTK) inhibitors, such as acalabrutinib and zanubrutinib, highlighting the Phase III ASPEN study (NCT03053440) and comparing outcomes and adverse events to those resulting from treatment with ibrutinib. Dr Castillo also talks on the use of non-covalent BTK inhibitors, such as pirtobrutinib, which have demonstrated efficacy in patients with Waldenström’s macroglobulinemia and disease progression. Additionally, Dr Castillo talks on ongoing clinical trials investigating combination approaches with the BCL-2 inhibitor venetoclax, an anti-CXCR4 agent ulocuplumab, and the small molecule inhibitor mavorixafor. This interview took place during the ninth annual meeting of the Society of Hematologic Oncology (SOHO 2021) congress.