Prognostic value of mayo 2012 vs. european‑modified mayo 2004 staging in AL amyloidosis patients with discordant stage classifications

Abstract Background: Systemic AL amyloidosis is a clonal plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains in vital organs, leading to progressive organ dysfunction. Accurate risk stratification at diagnosis is critical for guiding therapeutic decisions. The Mayo 2012 staging system incorporates cardiac biomarkers (troponin T, NT-proBNP) and the difference in serum free light chains (dFLC), whereas the European-modified Mayo 2004 system relies solely on cardiac biomarkers. Although both are widely used, direct head-to-head comparisons of their prognostic value are limited. We aimed to compare their prognostic performance in a real-world cohort of AL amyloidosis patients treated with bortezomib-based therapy, with a particular focus on those whose staging results were discordant between the two systems. Objectives: The objective of this study was to compare the prognostic predictive ability of the Mayo 2012 staging system and the European-modified Mayo 2004 system in patients with discordant staging results. Methods: We retrospectively analyzed 177 patients with systemic AL amyloidosis who were treated with bortezomib-based regimens between January 2020 and March 2025, all of whom were staged using both the Mayo 2012 and European-modified Mayo 2004 systems. Concordance was defined as identical risk categories after mapping stage 3 to 3A and stage 4 to 3B. Patients with discordant staging were identified for comparative analysis. Kaplan–Meier curves with log-rank tests were used to assess prognostic discrimination, and receiver operating characteristic (ROC) curves with corresponding area under the curve (AUC) values were generated to compare the ability of each staging system to predict organ responses. Results: In our cohort, 54% of patients were classified as concordant and 46% as discordant between the Mayo stage and the European modification. Among the 83 patients in the discordant group, 53 were male (64%) and 30 were female (36%), with a mean age of 65 years. For Mayo staging, heart involvement was observed in 85.7% of patients with stage 3 and 98.4% with stage 4, and kidney involvement in 55.4% and 36.5%, respectively. For the European modification, heart involvement was reported in 92.5% of patients with stage 3A and 96.4% with stage 3B, and kidney involvement in 47.3% and 42.9%, respectively, highlighting differences in organ involvement patterns between stages. To further assess the prognostic value of each staging system, overall survival curves were analyzed within the discordant group. Kaplan–Meier analysis showed that curves stratified by the Mayo stage exhibited significant overlap between stage 3 and stage 4 despite a significant log-rank p-value (p = 0.0066), indicating limited prognostic discrimination among higher-risk stages. In contrast, curves stratified by the European-modified Mayo 2004 system demonstrated clearer stepwise separation from stage 1 through stage 3B, with minimal overlap (log-rank p-value = 0.0011). Survival probabilities declined progressively across stages, with stage 3B showing markedly inferior outcomes compared with the others. Beyond survival, the European-modified system also showed superior performance in predicting organ responses within the discordant subgroup. It demonstrated significantly better discrimination for hematologic response compared with the Mayo stage (AUC 0.66 vs. 0.33, p = 0.0188) and notably stronger predictive ability for cardiac response (AUC 0.90 vs. 0.50, p = 0.0101). In contrast, no meaningful difference was observed between the two systems in predicting renal response (AUC 0.66 vs. 0.52, p = 0.3282). Conclusions: Although both the Mayo 2012 and European-modified Mayo 2004 staging systems were designed to predict prognosis based on organ involvement, previous studies had not clearly demonstrated which provided superior prognostic discrimination. In our analysis of AL amyloidosis patients with discordant staging, the European modification demonstrated superior prognostic discrimination compared with the Mayo 2012 system, with clearer separation of risk categories. These findings support the European modification as a more refined tool for prognostic assessment, particularly in challenging cases of AL amyloidosis.