Substratification of patients with newly diagnosed standard-risk multiple myeloma

Despite the absence of high-risk cytogenetics and lower International Staging System (ISS) stages, a subset of patients with multiple myeloma (MM) experience poor overall survival (OS). We studied 1461 patients with newly diagnosed MM to identify patient and disease characteristics that predict a high-risk phenotype among standard-risk patients. Fifty-six percent of all patients presented with standard-risk disease. Among them, advanced age, extremes of body mass index, non-hyperdiploid karyotype and abnormal lymphocyte counts were associated with worse OS. Standard-risk patients with 0-1 of these adverse factors (hazard ratio [HR] 032, 95% confidence interval [CI] 024-043, P<0001) and 2 adverse factors (HR 054, 95% CI 041-072, P<0001) experienced better OS than high-risk patients. Two or more adverse factors were present in 17% of standard-risk patients and were associated with OS comparable to high-risk patients (HR 091, 95% CI 067-124, P=0548). Predictive power among standard-risk patients was improved using score groups compared to ISS stages. Patients with standard-risk MM are a heterogeneous group with one in six patients experiencing OS comparable to high-risk disease. Patients at risk can be identified using readily available patient and disease characteristics. These findings emphasize the importance of accurate risk stratification and help explain part of the heterogeneity observed in clinical practice.