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ABSTRACTObjectives: There may be a shift in risk stratification at progression compared to that at diagnosis in patients with multiple myeloma (MM). We aimed to evaluate whether re-staging and stage migration is of prognostic impact.Methods: Real-world data from the National Longitudinal Cohort of Hematologic Diseases-multiple myeloma were collected; 263 consecutive patients demonstrating disease progression were finally included. Staging at diagnosis and re-staging at progression were performed using the International Staging System (ISS) and Revised International Staging System (RISS).Results: Based on ISS re-staging, the median post-progression survival (mPPS) of patients with stage I, II, and III was 44.2, 21.7, and 11.6 months, respectively (P < 0.0001). Based on RISS re-staging, the mPPS of patients with stage I, II, and III was 50.3, 22.2, and 11.4 months, respectively (P < 0.0001). The mPPS in patients with improved, maintained, and deteriorated ISS stage migration from diagnosis was 33.6, 20.9, and 16 months, respectively (P = 0.0051) and that with improved, maintained, and deteriorated RISS stage migration was 48.4, 23.1, and 13.9 months, respectively (P < 0.001). Compared to patients with maintained or improved disease stage, those with deteriorated ISS/RISS migration showed significantly higher incidence of Del(17P) at progression and worse PPS. Multivariate analyses indicated both re-staging and stage migration by ISS/RISS at progression were independent predictors for PPS.Conclusions: We demonstrated that ISS/RISS re-staging showed superior prognostic utility over ISS/RISS staging in predicting PPS. Patients with deteriorated stage migration or maintained advanced stage at progression may need more individualized treatment.