Prognostic impact of Dmax on baseline FDG-PET/CT in newly diagnosed multiple myeloma

This study aimed to evaluate the prognostic significance of FDG-PET/CT-derived biomarkers, including volumetric and dissemination metrics, in newly diagnosed multiple myeloma (NDMM). A total of 146 NDMM patients who underwent baseline FDG-PET/CT before any treatment between 2014 and 2022 at two institutions were retrospectively analyzed. Metabolic tumor burden was quantified using total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG), while spatial dissemination was assessed by the maximal interlesional distance (Dmax), defined as the greatest threedimensional Euclidean distance between lesion centroids. Lesions were segmented semi-automatically using LIFEx software with a 41% SUVmax threshold and a minimum SUV of 2.5. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and optimal cutoffs were determined using maximally selected rank statistics. Among PET-derived parameters, TMTV and Dmax were significantly associated with PFS and OS and retained independent prognostic value after adjustment for clinical and biological prognostic factors. In multivariate analysis performed in separate models due to collinearity, TMTV > 18.6 cm³ (PFS: HR = 2.17, p = 0.003; OS: HR = 2.23, p = 0.04) and Dmax > 23.2 cm (PFS: HR = 1.89, p = 0.01; OS: HR = 2.69, p = 0.01) remained independent prognostic factors. Dmax represents an independent PET-derived biomarker reflecting spatial disease dissemination in NDMM. The combined evaluation of dissemination and volumetric parameters may improve baseline risk stratification, providing a more comprehensive assessment of disease biology and potentially guiding therapeutic decisions in multiple myeloma.