New Validated Staging System for Light Chain (AL) Amyloidosis With Stage IIIC Defining Ultra-Poor Risk: AL International Staging System

作者：Jahanzaib Khwaja, Amy A. Kirkwood, Paolo Milani, Binoy Yohannan, Foteini Theodorakakou, Flores Weverling, Valeria Di Simone, Sriram Ravichandran, Shaji Kumar, Ιoannis Petropoulos, Roberta Mussinelli, Oliver Cohen, Marish I.F.J. Oerlemans, Eli Muchtar, Κimon Stamatelopoulos, Helen J. Lachmann, Julian D. Gillmore, Αlexandros Briasoulis, Morie A. Gertz, Carol Whelan, Lucia Venneri, Marianna Fontana, Shameem Mahmood, Rahel Schwotzer, Monique C. Minnema, Angela Dispenzieri, Giovanni Palladini, Efstathios Kastritis, Ashutosh Wechalekar · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco-25-02558 · 被引用次数：8 · 研究领域：Amyloidosis: Diagnosis, Treatment, Outcomes、Alzheimer's disease research and treatments、Intracerebral and Subarachnoid Hemorrhage Research

PURPOSE Outcomes in systemic light chain (AL) amyloidosis have improved with modern therapy limiting utility of existing risk stratification models. We validate a new staging system, incorporating longitudinal strain (LS) to the biomarker-based (NT-proBNP and Troponin-T) staging system in the contemporary treatment era (2015-2024). METHODS AL International Staging System (AL-ISS) was derived from a cohort of patients with AL amyloidosis from the UK National Amyloidosis Centre (2015-2019). The model was validated in patient cohorts from Europe (Greece, Italy, the Netherlands, and Switzerland), the United States (2015-2024), and the United Kingdom (2020-2024). RESULTS In total, 2,493 patients were included (derivation, n = 573; validation n = 1,920). In a multivariable model for the derivation cohort, LS ≥ –9% and cardiac biomarkers at previously validated thresholds (NT-proBNP 332 ng/L and 8,500 ng/L and high-sensitivity troponin T ≥ 50 ng/L) were independent poor prognostic factors stratifying patients into stages I, II, IIIA, IIIB, and IIIC. In the validation cohort, the patient stages were stage I: 317 (17%), II: 782 (41%), IIIA: 551 (29%), IIIB: 174 (9%), and IIIC: 96 (5%), respectively (first-line daratumumab treated: 826; 43%). With a median follow-up of 34 months, median overall survival (OS) was not reached (NR); estimated 1-year, 2-year, and 3-year OS was 82%, 74%, and 70% respectively. The median survival for stages I to II, IIIA, IIIB, and IIIC were NR, 67, 26, and ...