Outcomes Among <scp>MM</scp> Patients Receiving Early Intervention for <scp>MRD</scp> Progression Following Autologous Stem Cell Transplantation

Minimal residual disease (MRD) testing is essential for evaluating treatment response among multiple myeloma (MM) patients. Many patients experience MRD progression (MRD-P) before they meet the criteria for clinical or biochemical progression (PD), thus raising questions about the timing of treatment. In this retrospective study, the effect of early intervention (EI) on prognosis was investigated among 42 newly diagnosed MM patients who developed MRD-P after initial treatment with autologous stem cell transplantation. In the EI group (n = 9), treatment was modified at the onset of MRD-P; in the PD group (n = 33), treatment was delayed until disease progression occurred. At a median follow-up of 25 months, compared with the PD group, the EI group demonstrated a longer time to progression (median 34.8 months vs. 6.6 months, p = 0.029), superior overall survival (median not reached vs. 41.0 months, p = 0.034), and significantly higher MRD re-negativity rates (median 12.6 months vs. 75.9 months, p < 0.001). Multivariate analysis revealed that early intervention was significantly associated with improved MRD re-negativity (HR = 0.07; p = 0.001). This hypothesis-generating retrospective study demonstrated that early intervention at MRD-P onset was associated with improved survival outcomes and higher rates of MRD re-negativity in this cohort. Despite significant limitations, such as the small sample size, nonrandomized design, and unmeasured confounders, these findings provide preliminary data to inform the design of future prospective randomized trials.