Future Directions in the Frontline Management of Waldenström Macroglobulinemia

Abstract

Despite substantial progress in the clinical management of Waldenström's Macroglobulinemia (WM) and the emergence of chemotherapy-free approaches such as BTK inhibitors, WM is still a disease in which current treatments fail to cure and are in part associated with significant toxicities, compromising treatment outcome and quality of life. Thus, the vision for future front-line therapy should be to develop regimens which combine improved efficacy and excellent applicability with a low toxicity profile. Conventional immunochemotherapy such as bendamustine-rituximab is highly active but limited by hematotoxicity and long-lasting immunosuppression. Thus, further intensification of this treatment concept will most likely not be successful. Chemotherapy-free approaches such as BTK inhibitors have already changed the treatment landscape in WM, but still have major limitations such as the need for non-fixed duration treatment. Most probably, the combination of non-chemotherapy based, targeted approaches with different modes of action will ensure that we at least come closer to our vision of achieving functional cure in WM in the near future.

Keywords: BTK-inhibitors; Chemoimmunotherapy; Front-line; Treatment-naïve; Waldenstrom’s macroglobulinemia.