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

Jahanzaib Khwaja^1,2, Amy A Kirkwood³, Paolo Milani^4,5

¹National Amyloidosis Centre, Royal Free London, UCL, London, United Kingdom.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology

|December 7, 2025

Summary

This summary is machine-generated.

A new staging system for systemic light chain (AL) amyloidosis, incorporating longitudinal strain (LS) and cardiac biomarkers, accurately identifies patients with ultra-poor prognosis (Stage IIIC) in the modern treatment era.

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Area of Science:

Cardiology
Hematology
Medical Diagnostics

Background:

Systemic light chain (AL) amyloidosis outcomes have improved with contemporary therapies.
Existing risk stratification models may have limited utility in the current treatment landscape.

Purpose of the Study:

To validate a novel staging system for AL amyloidosis.
To incorporate longitudinal strain (LS) into biomarker-based staging.
To assess the system's performance in the contemporary treatment era (2015-2024).

Main Methods:

The AL International Staging System (AL-ISS) was derived from a UK cohort (2015-2019).
Validation was performed using international patient cohorts from Europe and the US (2015-2024).
Longitudinal strain (LS) and cardiac biomarkers (NT-proBNP, Troponin-T) were analyzed.

Main Results:

The AL-ISS includes LS ≥ -9% and specific cardiac biomarker thresholds.
The system stratified patients into stages I, II, IIIA, IIIB, and IIIC.
Stage IIIC independently predicted the poorest outcomes, with a median survival of 7 months.
External validation demonstrated good predictive performance (Harrell C 0.69).

Conclusions:

A new, validated staging system for AL amyloidosis has been established.
The system effectively identifies an ultra-poor risk group (Stage IIIC).
This tool aids prognostication in patients receiving contemporary treatments.