Sustained MRD Negative for 4 Years Is a Significant Marker of Prognosis in Patients with High-Risk Multiple Myeloma

Background/Objectives: The optimal duration of maintaining minimal residual disease (MRD) negative status remains unclear in transplant-eligible newly diagnosed multiple myeloma (TE-NDMM). This single-center retrospective study aimed to explore the minimum duration of sustained MRD negativity with prognostic value. Methods: This research included 223 TE-NDMM patients who achieved at least two consecutive MRD-negative assessments after initial treatment. We analyzed the influence of sustained MRD negativity on survival in different risk stratifications. Results: There was no difference in progression-free survival (PFS) between high-risk (HR) patients with an MRD negativity duration of ≥2 years and patients in the standard-risk (SR) group (70.77 vs. 67.38 months, p = 0.529). In SR patients, PFS showed no significant difference between patients maintaining MRD negativity for 2–3 years and those maintaining MRD negativity for more than 3 years (72.25 months vs. 107.50 months, p = 0.103). In contrast, in the HR group, there was no difference between a duration of 4–5 years and ≥5 years (NR vs. 84.53 months, p = 0.136). A duration over 2 years was associated with superior overall survival (OS) for all patients. Conclusions: Long-term maintenance of MRD-negative status was associated with good prognosis. Sustained MRD negativity for ≥2 years was associated with reducing the adverse influence of high-risk cytogenetics, and a duration over 4 years may be correlated with longer PFS in high-risk multiple myeloma patients in an exploratory analysis based on limited cases.