Multiple Myeloma Precursor Disease

Recent data indicate that multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma. Currently, multiple myeloma is a clinical diagnosis based on manifestations including hypercalcemia, renal failure, anemia, and bone lesions, whereas MGUS and smoldering myeloma are diagnosed based on laboratory abnormalities. Current clinical markers allow for more individualized risk stratification and counseling of these patients. However, there is a dearth of biomarkers and molecular imaging techniques capable of (1) accurately identifying patients with disease biology corresponding with high risk of progression; (2) elucidating the mechanism of transformation to multiple myeloma; and (3) forming a framework for development of targeted therapies. This case presentation and review discusses the current understanding of myeloma precursor disease and future opportunities for improving personalized management of patients with MGUS or smoldering myeloma, as well as the potential for developing early treatment strategies designed to delay and prevent development of multiple myeloma. JAMA. 2010;304(21):2397-2404 www.jama.com