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

Summary 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.