This study aimed to evaluate the existing staging systems for multiple myeloma (MM) in the real world. From January 2010 to June 2019, we retrospectively analyzed 859 newly diagnosed MM patients from two institutions. Clinical data including laboratory findings, imaging examinations and staging system were obtained by reviewing medical records. Survival distributions were estimated using the Kaplan–-Meier curve analysis, and Cox proportional hazards model were used to identified risk factors. The overall survival (OS) of eligible patients was 61.0 months. The Revised International Staging System (R-ISS) had a larger receiver operating characteristic curve area (0.603) than both the International Staging System (0.573) and the Durie Salmon staging system (0.567). In the group receiving immunomodulatory agents-based regimens, the median OS was 92.0 months in R-ISS I, 63.0 months in R-ISS II and 18.0 months in R-ISS III (p<0.0001). In the group receiving proteasome inhibitors-based regimens, the median OS was 102.0 months in R-ISS I, 63.0 months in R-ISS II and 22.0 months in R-ISS III (p<0.0001). In different subgroups grouped according to age, HGB, CREA, and Ca, R-ISS also had a good stratification effect. Patients in R-ISS II, which accounted for 69.9% of all patients, were further analyzed. Univariate and multivariate Cox analyses revealed that age >65 years (p=0.001), HGB < 100 g/L (p<0.001), elevated LDH (p=0.001), and Ca (p=0.010) were independent predictors of worse prognosis within R-ISS II. To conclusion, R-ISS remains a valuable staging system in the real world of the novel drug era. However, patients classified as R-ISS II still have great heterogeneity.

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