AL-ISS: A validated international staging system for AL amyloidosis

The development and external validation of a novel international staging system for light chain (AL) amyloidosis were reported by Khwaja et al. in the Journal of Clinical Oncology. The model was derived and validated in 2,493 patients (derivation, n = 573; validation, n = 1,920), using overall survival (OS) to evaluate prognostic accuracy.

Key data: The AL International Staging System (AL‑ISS) integrates N-terminal pro–B-type natriuretic peptide (NT‑proBNP), high-sensitivity troponin T (hs‑TnT), and echocardiographic longitudinal strain (LS) to refine risk stratification. Among patients with elevated cardiac biomarkers (NT‑proBNP ≥8,500 ng/L and hs‑TnT ≥50 ng/L), LS further stratified risk, identifying an ultra-poor-risk group (Stage IIIC) with a median overall survival (OS) of 7 months despite modern therapy. Median OS was not reached for Stages I–II, 67 months for IIIA, and 26 months for IIIB.

Key learning: AL-ISS integrates LS alongside established cardiac biomarker staging, enabling more granular risk stratification in AL amyloidosis and defining a newly recognized Stage IIIC subgroup with ultra-poor-risk disease.