Toward personalized treatment in Waldenstrom macroglobulinemia

Waldenstrom macroglobulinemia (WM) is a rare lymphoma with 1000 to 1500 new patients diagnosed per year in the United States. Patients with WM can experience prolonged survival times, which seem to have increased in the last decade, but relapse is inevitable. The identification of recurrent mutations in the MYD88 and CXCR4 genes has opened avenues of research to better understand and treat patients with WM. These developments are giving Tway to personalized treatment approaches for these patients, focusing on increasing depth and duration of response alongside lower toxicity rates. In the present document, we review the diagnostic differential, the clinical manifestations, and the pathological and genomic features of patients with WM. We also discuss the safety and efficacy data of alkylating agents, proteasome inhibitors, monoclonal antibodies, and Bruton tyrosine kinase inhibitors in patients with WM. Finally, we propose a genomically driven algorithm for the treatment of WM. The future of therapies for WM appears bright and hopeful, but we should be mindful of the cost-effectiveness and long-term toxicity of novel agents.