Ki-67 Proliferation Index Improves the Prognostic Stratification Accuracy of International Staging System in Newly Diagnosed Multiple Myeloma

Objective: To investigate the clinical characteristics and prognostic significance of distinct Ki-67 proliferation indices in patients with newly diagnosed multiple myeloma (NDMM). Methods: A retrospective analysis of clinical data from 307 NDMM patients admitted to the Second Hospital of Shanxi Medical University from January 2015 to December 2023. Patients were stratified into two cohorts based on Ki-67 proliferation index: Ki-67 > 10% and Ki-67 ≤ 10%. Results: Among the 307 enrolled NDMM patients, 199 (64.82%, 199/307) were assigned to the Ki-67 ≤ 10% group. The median progression-free survival (mPFS) was 45.52 months (95% CI: 39.40–51.66) in the Ki-67 ≤ 10% group, compared with 25.81 months (95% CI: 20.61–31.00) in the Ki-67 > 10% group, with a statistically significant difference in PFS between the two cohorts (p < 0.001). Between these two groups, the median Overall Survival (mOS) reached 61.61 months (95% CI: 54.48–68.74) in the Ki-67 ≤ 10% group and 34.78 months (95% CI: 28.89–40.66) in the Ki-67 > 10% group, with a statistically significant difference in OS between the two cohorts (p < 0.001). Multivariate Cox proportional hazards regression analysis demonstrated that the Ki-67 proliferation index served as an independent prognostic factor for both PFS (HR:1.227; 95% CI: 1.097–1.743; p = 0.043) and OS (HR:1.192; 95% CI: 1.169–1.847; p = 0.048) in patients with NDMM. Subsequently, patients with NDMM were stratified into three risk groups based on the combination of International Staging System (ISS) stage and Ki-67 proliferation index. A total of 103 patients (33.55%) were classified into group I, 138 patients (44.95%) into group II, and 66 patients (21.50%) into group III. Survival analyses revealed significant differences in survival outcomes across the three combined staging groups. The mPFS was 49.74 months (95% CI: 28.81–63.19) in group I, 35.00 months (95% CI: 24.82–45.18) in group II, and 17.00 months (95% CI: 13.94–20.06) in group III patients, with a statistically significant inter-group difference in PFS (p = 0.011). Meanwhile, the mOS of the three groups was 71.38 months (95% CI: 63.59–79.17), 59.51 months (95% CI: 51.74–67.28), and 26.64 months (95% CI: 22.31–30.98), respectively. There was an obvious significant difference in OS among the three groups (p < 0.001). Conclusions: NDMM patients with Ki-67 proliferation index > 10% have a significantly worse prognosis than those with Ki-67 ≤ 10%. A high Ki-67 index (>10%) is identified as an independent adverse prognostic parameter for NDMM. Furthermore, the integration of Ki-67 proliferation index with ISS staging can substantially enhance the accuracy of prognostic risk stratification in patients with NDMM.