Prognostic value of a combined systemic immune-inflammation index and prognostic nutritional index score for risk stratification in newly diagnosed multiple myeloma: a retrospective cohort study

Background: Systemic inflammation and nutritional impairment may complement established staging in newly diagnosed multiple myeloma (NDMM). A pretreatment score integrating the systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) was developed and internally validated for progression-free survival (PFS) and overall survival (OS) risk stratification. Methods: This retrospective cohort included 164 patients with NDMM treated between 2017 and 2024. Cutoffs were derived from 36-month PFS cumulative/dynamic receiver operating characteristic curves using inverse probability of censoring weighting (IPCW), and a 0-2-point SII-PNI score was constructed. Survival associations, time-varying PFS effects, bootstrap internal validation, calibration, and incremental value beyond age and the Revised International Staging System (R-ISS) were evaluated. Additional analyses examined four SII-PNI phenotypes and adjustment for treatment and clinical factors. Results: Cutoffs were 382.34 for SII and 35.40 for PNI. PFS and OS differed across score groups (both P < 0.001), and the PFS association was strongest early and attenuated over time. Relative to the low-SII/high-PNI phenotype, adjusted PFS hazard ratios were 1.997 for high SII alone, 2.052 for low PNI alone, and 11.416 for concurrent high SII and low PNI; corresponding OS hazard ratios were 2.986, 2.998, and 10.292. In the 2022–2024 temporal validation cohort, the Harrell C-index for PFS was 0.519 for age plus R-ISS and 0.777 after addition of the development-derived score. Conclusion: Higher pretreatment SII-PNI scores were associated with poorer PFS and OS in patients with NDMM. The SII-PNI score may provide complementary prognostic information and help refine risk stratification beyond conventional staging.