Advances in Treatment of Waldenström Macroglobulinemia

The discovery of recurring somatic mutations, in particular MYD88 and CXCR4 mutations, in Waldenström macroglobulinemia (WM), a rare B-cell lymphoproliferative disorder, led in the last decade to the development of several therapeutic agents with high efficacy. This review aims to provide an overview of available treatments in WM and novel agents, focusing on studies published over recent years.

There is no international consensus on the best first-line option in treatment-naïve patients. Randomized clinical trials are rare in WM and there has been no prospective comparison of chemoimmunotherapy and BTK inhibitors in the frontline setting. Chemoimmunotherapy and BTK inhibitors, the two feasible and most widely used treatments in first-line treatment, represent very different options in terms of duration of therapy, route of administration, cost, and adverse effect. In addition to tumor genotype and patient comorbidities, choice of therapy in WM should take into account these parameters. Results of ongoing and future clinical trials evaluating fixed-duration combinations with BTK inhibitors and novel agents are awaited.