Comparison of Alternative Mayo Staging Classification Systems USED in LIGHT-Chain Amyloidosis

Background: Light chain amyloidosis (AL), a rare, life-threatening disorder, is characterized by deposition of abnormal amyloid fibrils in various organs, notably the heart. Morbidity and mortality in AL patients are closely linked to the magnitude of heart involvement. The Mayo staging system is widely used for stratifying the severity and prognosis of patients with AL. The initial approach, developed in 2004 (Mayo 2004), was later revised into two separate approaches (Mayo 2004 European, Mayo 2012). Currently, no consensus exists on which staging system to use, with clinical trials utilizing either European Modification Mayo 2004 or Mayo 2012 as part of their patient inclusion criteria.

Objectives: This study aimed to characterize the most severe AL patients using different Mayo staging systems and to determine the agreement between European Modification Mayo 2004 and Mayo 2012.

Methods: A cross-sectional analysis (July 1, 2017 - June 30, 2023) was conducted using an anonymized dataset from the TriNetX Dataworks comprising about 95 million patients from 57 USA healthcare organizations. Adults diagnosed with AL between January 1, 2018, and December 31, 2022, with ≥2 records for AL (ICD-10-CM code E85.81) ≥30 days apart were included. Characteristics of interest, including organ involvement (i.e. cardiac, renal, hepatic), the Charlson Comorbidity Index (CCI) and lab values required for staging (NT-proBNP, cTNT, and dFLC) were captured ±180 days from AL diagnosis (ICD-10 E85.81). All patients with available data were staged according to the classification systems under comparison.

Results: Among 525 AL patients, 54.3% (n=285) and 54.1% (n=284) were classified as severe AL according to European Modification Mayo 2004 (stages IIIa: 29.9%; IIIb: 24.4%) and Mayo 2012 (stages III: 41.9%; IV: 12.2%), respectively. Most severe AL patients were predominantly male (65.6%/70.3%) with a mean age of 67.4/67.5 years, and mean CCI of 4/3 in stage IIIb (European Modification Mayo 2004) or stage IV (Mayo 2012), respectively. Renal involvement was observed in 76.6% / 56.2% and liver involvement in 8.6% / 4.7% of stage IIIb/IV patients. The overall agreement for all stages between the two systems was 46.8% (246 out of 525 patients), indicating low concordance.

Conclusion: Our findings reveal a notable lack of agreement among the AL Mayo staging systems. Given developments in the standard-of-care for AL since their inception, it is crucial to re-evaluate the prognostic value of these staging systems in the context of contemporary and upcoming treatments.

Laires:Alexion / AstraZeneca: Current Employment. Thompson:Alexion, AstraZeneca Rare Disease: Current Employment. Catini:Alexion, AstraZeneca Rare Disease: Current Employment. Manwani:Alexion / AstraZeneca: Current Employment. Zhang:Alexion / AstraZeneca: Current Employment. Yang:Alexion / AstraZeneca: Current Employment.