Abstract Body (Do not enter title and authors here): Introduction
AL cardiac amyloidosis (AL-CA) is marked by extracellular deposition of misfolded immunoglobulin light chains, leading to cardiac dysfunction and increased mortality. The Revised Mayo staging system, incorporating cardiac biomarkers, is widely used to assess disease severity and guide treatment. Graded cardiac response to therapy, which reflects changes in cardiac biomarkers, has emerged as an effective prognostic tool beyond baseline staging. This study aims to describe clinical and cardiac biomarker profiles across Mayo stages and to validate the association between graded cardiac response at serial timepoints and survival after first-line therapy.

Methods
We retrospectively analyzed patients diagnosed with AL-CA at the Cleveland Clinic Foundation (CCF) between January 2012 and December 2022, excluding those with missing demographics or non-AL amyloidosis cases. The Overall Response Rate (ORR) was calculated as a composite outcome of the graded cardiac responses to front-line therapy as follows: complete response (CR) + very good partial response (VGPR) + partial response (PR)

Results
We included 411 patients (63.7% male, 78.6% white; median age 68 years (IQR: 31–92). Mayo stages distribution was stage I (3.6%), II (12%), III (27.7%), and IV (56%). NYHA class III was prevalent in Mayo stages III and IV (45.4% and 44.7%, respectively), whereas Mayo stage II patients were mostly NYHA class II (45%; p=0.007). NT-proBNP and Troponin T increased significantly with advancing stage (p<0.001). LVEF was highest at Mayo stage II (60%) and lowest at stage IV (52%; p<0.001) (Table 1). Treatment regimens included Dara CyBorD (19%), CyBorD (54%), Daratumumab alone (3.5%), and VD/RD (18%). ORR improved progressively from 32.4% at 3 months to 94% at 24 months (Figure 1). Survival analysis indicated a significant correlation between response rate at 12–18 months and improved survival (log-rank p=0.024). Response assessments at earlier (0–3 months, p=0.18; 3–6 months, p=0.64; 6–12 months, p=0.29) and later (18–24 months, p=0.06) intervals were not significantly associated with survival (Figure 2).

Conclusions
Advanced Mayo stages correlate with higher biomarker burden, reduced LVEF, and greater diastolic dysfunction. Although cardiac response rates generally improve over time, only responses assessed at mid-term intervals (12–18 months) significantly predict improved survival outcomes, highlighting the importance of achieving early therapeutic response in AL-CA