Prognostic value of minimal residual disease detected by EuroFlow next-generation flow cytometry and next-generation sequencing in patients with multiple myeloma achieving complete response and receiving lenalidomide maintenance after autotransplant: a prospective comparison study.

Novel agents inducing deeper responses have improved the prognosis of patients with multiple myeloma (MM). To assess minimal residual disease (MRD) and stratify patients achieving complete response (CR), advanced technologies such as EuroFlow next-generation flow cytometry (NGF) and next-generation sequencing (NGS) are increasingly utilized. This prospective study evaluated responses in newly diagnosed MM patients undergoing autologous stem cell transplantation (ASCT) followed by lenalidomide maintenance therapy across multiple Japanese medical centers. Patients achieving CR or stringent CR within 100-365 days post-ASCT were included. MRD levels in the bone marrow were assessed using both NGF and NGS (cutoff: 1×10-5) at three time points: 100-365 days, 1 year, and 2 years post-ASCT. A total of 52 patients were analyzed. MRD levels determined by NGF and NGS showed a strong correlation (r=0.9722; P<0.0001). After a median follow-up of 3 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 76.5% (95% confidence interval [CI]: 62.3-85.9%) and 96.2% (95% CI: 85.5-99.0%), respectively. Patients with sustained MRD negativity for >6 months demonstrated superior 3-year PFS compared to those without sustained MRD negativity, as measured by both NGF (100% vs. 67.6%; hazard ratio [HR] =0.06; 95% CI: 0.0005-0.50; P<0.007) and NGS (90.5% vs. 72.2%; HR=0.23; 95% CI: 0.06-0.94; P=0.048). These findings highlighted a strong correlation in the MRD levels assessed by NGF and NGS and validated that sustained MRD negativity was significantly associated with prolonged PFS (clinical trial registered at UMIN 000022238).