Risk stratification in multiple myeloma, part 1: characterization of high-risk disease

Survival in multiple myeloma (MM) is variable, ranging from several months to more than 15 years. While survival has recently improved with the use of novel therapy, approximately 25% of patients have a median survival of 2 years or less. Accurate identification of high-risk patients, and risk stratification, are crucial in improving outcomes for all patients. In the first part of this two part series, we review the currently identified prognostic factors characterized by disease burden (Durie-Salmon staging system, International Staging System, magnetic resonance imaging, (18F) fluorodeoxyglucose positron emission tomography, presence of extramedullary disease or plasma-cell leukemia), host factors (age, performance status, and renal function), tumor biology (proliferation rate, conventional cytogenetics, interphase fluorescence in situ hybridization, and gene expression profiling), and depth of response to therapy. Efforts have been made to identify ultra-high-risk patients by combining all the identified variables into a unifying comprehensive model. In the second part of this series, we will discuss the significance of these factors in the context of currently available therapies for MM, distinguishing between treatments that only improve outcomes of high-risk patients when compared with previous therapies, versus those that overcome high-risk status, thereby reclassifying these patients as standard risk.