Baseline and early changes in circulating Serum Amyloid A (SAA) predict survival outcomes in advanced non-small cell lung cancer patients treated with Anti-PD-1/PD-L1 monotherapy

Systemic inflammation plays an important role in carcinogenesis and is associated with overall survival in patients with different cancer types, including those treated with immune checkpoint blockade (ICB). Serum Amyloid A (SAA) is an acute-phase protein and a marker of persistent inflammation. We hypothesized that circulating SAA may predict outcomes in advanced non-small cell lung (aNSCLC) patients treated with PD-1/PD-L1 ICB.This retrospective study included 91 aNSCLC patients who received anti-PD-(L)1 monotherapy in Sun Yat-sen University Cancer Center (Guangzhou, China) between August 2016 and June 2018. We examined the impact of circulating SAA at baseline and 8 (±2) weeks later on overall survival (OS). X-tile program was used to determine the cut-off values which optimized the significance of the split between Kaplan-Meier survival curves. Kaplan-Meier methodology and Cox regression analyses were conducted for survival analyses.The optimal cut-off value of baseline SAA for OS stratification was 137.6 mg/L. In univariate analysis, both high level of baseline SAA (hazard ratio [HR], 2.76; 95% confidence interval [CI], 1.47-5.18; P = 0.002) and lack of early SAA descent (HR, 1.51; 95% CI, 1.11-2.06; P = 0.009) were significantly associated with inferior OS. In multivariate analysis, gender, smoking status, performance status, liver metastasis, neutrophil-to-lymphocyte ratio, baseline SAA and early changes in SAA independently predicted OS (all with P < 0.05). A combined baseline SAA ≥ 137.6 mg/L and without early SAA descent identified a small cohort with remarkably worse OS (median, 3.2 months).Both high baseline and lack of early decline in circulating SAA are significantly associated with inferior outcomes in aNSCLC patients treated with PD-1/PD-L1 ICB. Combined these two SAA indexes provided improved risk stratification. The prognostic value of this simple, readily-available, and cost-effective biomarker warrants larger, prospective validation before definitive recommendation can be made.