Prognostic Value of Next‐Generation Flow Cytometry Versus Dual‐Tracer PET / CT for Minimal Residual Disease Assessment in Multiple Myeloma

ABSTRACT To evaluate the comparative prognostic utility of next‐generation flow cytometry (NGF) and dual‐tracer PET/CT in measuring minimal residual disease (MRD), this prospective real‐world study enrolled 118 newly diagnosed multiple myeloma (NDMM) patients. Patients underwent post‐treatment assessment using NGF (sensitivity 10 −5 ) and dual‐tracer PET/CT using 11 C‐acetate (AC‐PET) and 18 F‐FDG. While AC‐PET showed a numerically higher detection rate compared to FDG‐PET in paired analyses ( n = 45), a significant discordance was observed between imaging and immunophenotypic assessment. NGF detected MRD in 38.2% of paired cases compared to 11.8% by AC‐PET; however, AC‐PET uniquely identified metabolic activity in extramedullary sites for two NGF‐negative patients, highlighting the value of functional imaging in resolving spatial heterogeneity. In the landmark survival analysis ( n = 104), NGF positivity was identified as a robust independent predictor for inferior progression‐free survival (HR 2.21, 95% CI 1.01–4.81; p = 0.046) and overall survival (HR 4.97, 95% CI 1.23–20.01; p = 0.026), transcending baseline risk stratifications. Furthermore, longitudinal monitoring revealed that patients achieving sustained MRD negativity experienced significantly superior outcomes compared to those with transient negativity or persistent disease. These findings establish NGF as the standard prognostic biomarker for MM, while AC‐PET serves as a critical complementary tool for detecting extramedullary escape, supporting a risk‐adapted MRD strategy that integrates molecular depth with metabolic imaging.