Prognostic significance of dynamic minimal residual disease trajectories in newly diagnosed multiple myeloma.

While minimal residual disease (MRD) is a well-recognized prognostic marker in multiple myeloma (MM), the clinical significance of dynamic MRD trajectories and MRD-driven therapies remains incompletely elucidated. This retrospective study analysed serial MRD results from 231 newly diagnosed multiple myeloma (NDMM) patients who achieved ≥ complete remission (CR). MRD negativity independently predicted superior progression-free survival (PFS) (hazard ratio [HR] = 0.222; 95% confidence interval [CI] 0.124-0.400, p < 0.001) and overall survival (OS) (HR = 0.280; 95% CI 0.097-0.809, p = 0.019). Sustaining MRD negativity for ≥6 months improved OS (p < 0.001), while negativity duration ≥12 months conferred dual prognostic benefits for both PFS and OS (both p < 0.001). Patients with late MRD conversion (after ≥12 months of negativity) had OS comparable to those with sustained negativity (p = 0.339). Elevated circulating plasma cell at diagnosis (HR = 3.761; 95% CI 1.225-11.550, p = 0.021), failure to achieve MRD negativity post-induction (HR = 2.886; 95% CI 1.065-7.819, p = 0.037), and a high abnormal PC/BMPC% at MRD conversion (HR = 4.091; 95% CI 1.429-11.701, p = 0.009) were independent risk factors for progression post-conversion. These findings demonstrate the prognostic significance of sustained MRD negativity and support serial MRD monitoring as a potential basis for individualized MRD-driven treatment strategies in NDMM.