AbstractAs cardiac involvement is the most important prognostic marker in light-chain amyloidosis (AL), revised Mayo staging for AL incorporated N-terminal pro-brain natriuretic peptide (NTproBNP) and troponin T (TnT). However, prognostic value of novel biomarkers, such as soluble suppression of tumorigenicity 2 (sST2), growth differentiation factor 15 (GDF15), or osteopontin (OPN) is unknown in AL amyloidosis. We aimed to investigate additive predictive effects of novel biomarkers for overall mortality rates of AL amyloidosis patients. Levels of sST2, GDF15, and OPN were quantified at diagnosis in a total of 73 AL amyloidosis patients at Samsung Medical Center from 2010 to 2016. The median follow-up duration of the censored cases was 18.0 (12.4–28.1) months. A total of 25 deaths occurred during the follow-up period. Two novel biomarkers, sST2 and GDF-15 showed satisfactory predictive performances for both one-year and overall survival from ROC analysis. Best cut-off values for predicting one-year mortality were selected. Elevated sST2 and GDF-15 levels showed significant incremental prognostic values in addition to NT-ProBNP and TnT for overall mortality. Patients were assigned 1 point for elevated sST2 or GDF-15. The mean values of NT-proBNP, TnT, mean LV wall thickness, and septal e′ velocity differed significantly according to the scores. Patients with higher scores showed significantly worse prognosis even in patients with advanced revised Mayo staging. Two novel biomarkers, sST2 and GDF-15, showed satisfactory prognostic value for overall survival of AL amyloidosis patients. Furthermore, sST2 and GDF-15 showed additive incremental values over conventional biomarkers and further discriminated prognosis of patients in advanced stages.