Abstract / Summary
Background/Objectives: The Endothelial Activation and Stress Index (EASIX) is an easily accessible biomarker reflecting endothelial stress and has demonstrated prognostic value in several hematologic settings. However, its role in newly diagnosed multiple myeloma (NDMM), particularly according to the timing of assessment, remains insufficiently chara cterized. We evaluated the prognostic value of EASIX measured at diagnosis and immediately before autologous stem cell transplantation (autoSCT) for overall survival (OS) and progression-free survival (PFS). Methods: This retrospective single-center study included 99 transplant-eligible patients with NDMM who underwent autoSCT between 2017 and 2023. EASIX was calculated at diagnosis and pre-autoSCT and log2-transformed. Survival was assessed using Kaplan–Meier analysis and Cox proportional hazards regression. Optimal EASIX thresholds were explored using maximally selected log-rank statistics. Model discrimination was evaluated using Harrell’s concordance index and time-dependent area under the curve (AUC). Results: EASIX at diagnosis was available for 92 patients. Higher log2(EASIX) at diagnosis remained associated with inferior OS after adjustment for International Staging System (ISS) stage (HR 1.38, 95% CI 1.11–1.71; p = 0.0035). It also remained associated with shorter PFS after adjustment for ISS stage, age, and sex (HR 1.41, 95% CI 1.14–1.74; p = 0.001). Diagnosis EASIX demonstrated good discrimination for OS, with a C-index of 0.78 and sustained time-dependent AUC values. Conversely, pre-autoSCT EASIX was not significantly associated with OS or PFS when analyzed continuously, and cutoff-based analyses did not provide a consistent, robust prognostic signal. Conclusions: EASIX measured at diagnosis was associated with both OS and PFS in transplant-eligible NDMM, whereas continuous pre-autoSCT EASIX showed no consistent association with either outcome. A direct paired comparison demonstrated a significantly stronger prognostic association of diagnosis EASIX with PFS, while the corresponding between-timepoint difference for OS was not statistically significant. These findings support further evaluation of EASIX timing in larger independent cohorts.