Ruili Yuan, Jingjing Yin, Juan Liu, Ni Liu, Xuan Guo, Xiaoqin Wang
Dynamic changes in inflammatory and bone metabolic markers effectively reflect treatment response in MM. The dNLR and dBCTX were identified as independent prognostic factors of OS that represent immune function and bone repair. In a temporally independent cohort, the blood-derived markers were validated, supporting their clinical utility for disease monitoring and risk stratification.
OBJECTIVE: To investigate the clinical value of dynamic changes in inflammatory (NLR, PLR, LMR) and bone metabolic markers (β-CTX, PINP, BALP, serum calcium) before and after treatment for disease monitoring and prognosis in multiple myeloma (MM), and to validate these indicators in an independent cohort.
METHODS: A derivation cohort (2018-2021, n = 402) and a temporal validation cohort (2021-2023, n = 218) were retrospectively enrolled. Patients were stratified into remission (n = 260) and non-remission (n = 142) groups. Dynamic changes (Δ) in inflammatory and bone metabolic markers were compared between groups. ANC and ALC were analyzed to elucidate NLR dynamics. Univariate Cox regression, collinearity diagnostics, and time-varying Cox regression were used to identify prognostic variables. Sensitivity analyses and external validation were performed.
RESULTS: ΔPLR, ΔLMR, Δβ-CTX, ΔPINP, ΔBALP, and Δserum calcium differed significantly between groups (all P < 0.001), while ΔNLR did not (P = 0.616). Δβ-CTX showed the largest effect size. The derived neutrophil-to-lymphocyte ratio (dNLR) (HR 0.691, P < 0.001) and derived β-C-terminal telopeptide of type I collagen (dBCTX) (HR 4.205, P < 0.001) were independently associated with overall survival (OS). dNLR exhibited a time-dependent effect strengthening over follow-up, with pronounced prognostic value in R-ISS stage III patients (P < 0.001). Post-treatment ALC was also associated with OS (HR 0.767, P < 0.001). Results were confirmed in the validation cohort (dNLR: HR 0.595; dBCTX: HR 3.911; both P < 0.001).
CONCLUSION: Dynamic changes in inflammatory and bone metabolic markers effectively reflect treatment response in MM. The dNLR and dBCTX were identified as independent prognostic factors of OS that represent immune function and bone repair. In a temporally independent cohort, the blood-derived markers were validated, supporting their clinical utility for disease monitoring and risk stratification.