The Prognostic Significance of Dynamic Monitoring of Minimal Residual Disease Status in Patients with Multiple Myeloma: A Real-World Study.

Background: Minimal residual disease (MRD) is an established prognostic factor in multiple myeloma (MM), but the significance of dynamic MRD changes before and after autologous stem cell transplantation (ASCT) remains unclear. Methods: We retrospectively analysed 335 newly diagnosed MM patients who underwent upfront ASCT. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence interval (CI), adjusting for clinical risk factors. Results: Patients were classified as having persistent MRD negativity (n = 82, 24.5%), MRD- to MRD+ conversion (n = 40, 11.9%), MRD+ to MRD- conversion (n = 168, 50.1%), or persistent MRD positivity (n = 45, 13.4%). Median OS was not reached: 105, 131, and 87 months for the groups (p < 0.001); and PFS was not reached: 50, 71, and 38 months (p < 0.001). In multivariable analysis, persistent MRD positivity (HR, 4.762; 95% CI, 2.151-10.546; p < 0.001) and MRD- to MRD+ conversion (HR, 3.925; 95% CI, 1.791-8.598; p < 0.001) were associated with increased mortality risk compared with persistent MRD negativity, whereas MRD+ to MRD- conversion showed a borderline-significant increase (HR, 1.973; 95% CI, 0.963-4.046; p = 0.063). In addition, similar patterns were observed for PFS. In subgroup analyses, late MRD+ to MRD- conversion was associated with inferior PFS (HR, 1.857; 95% CI, 1.136-3.034; p = 0.014), whereas MRD- to MRD+ conversion showed no differences in OS or PFS (all p > 0.05). Among persistent MRD-positive patients, stable or increasing MRD pattern predicted worse outcomes (HR, 4.397; 95% CI, 1.190-16.240; p = 0.026). Conclusions: Longitudinal MRD trajectories provided independent prognostic information beyond static MRD assessment in MM. Subgroup analyses further suggest that dynamic MRD assessment might help refine risk stratification after ASCT.