Current and new approaches to the treatment landscape for adults with Waldenström macroglobulinemia

INTRODUCTION: Waldenström macroglobulinemia (WM) is an indolent B-cell lymphoma with unique clinical manifestations driven by both tumor infiltration of the bone marrow and extramedullary tissues, as well as IgM-related pathology. Recent therapeutic advances for WM have been largely driven by molecular discoveries, and current agents have significantly improved disease control and progression-free survival. However, WM remains incurable, and novel treatment strategies that balance efficacy with tolerability are needed. AREAS COVERED: This review summarizes current treatment approaches, including chemoimmunotherapy and Bruton tyrosine kinase inhibitors, and discusses emerging therapeutic strategies with a focus on clinical efficacy, toxicity, and evolving treatment paradigms. We also examine the role of combination approaches and novel agents, considering their potential integration into the current treatment landscape. EXPERT OPINION: Despite substantial progress, key challenges remain, including the absence of definitive comparative data between various treatment strategies, the optimal sequencing of available agents, and an understanding of the impact of novel therapies on the depth of hematologic response, as well as long-term clinical and patient-reported outcomes. Future efforts should focus on biologically informed treatment selection and the development of strategies that reduce cumulative toxicities while achieving durable disease control.