Early kinetics of serum amyloid A predict clinical benefit to first-line chemoimmunotherapy and immunotherapy in advanced non-small cell lung cancer: a retrospective analysis

Abstract

Abstract Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for advanced non-small cell lung cancer (NSCLC), yet durable responses remain limited in a subset of patients. Serum amyloid A (SAA), an acute-phase protein linked to systemic inflammation, may reflect dynamic immune responses. This retrospective study analyzed 242 advanced NSCLC patients treated with first-line chemoimmunotherapy or immunotherapy between August 2016 and December 2024. Patients were stratified by early SAA kinetics into flare-responders (initial rise followed by decline), responders (sustained decline), and non-responders. Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were evaluated using Kaplan–Meier and Cox regression analyses. In the chemoimmunotherapy cohort, SAA flare-responders demonstrated significantly prolonged median PFS (29.8 months, 95% CI: 9.95—49.65; HR: 0.31, 95% CI: 0.15–0.64; p < 0.01) compared to non-responders (7.4 months, 95% CI: 4.67—10.13). Similarly, in the immunotherapy cohort, SAA flare-responders showed superior PFS. (19.9 vs. 2.1 months, HR 0.31, p < 0.01). Multivariate analysis confirmed early SAA kinetics as an independent prognostic factor for both PFS and OS in both treatment groups. Early SAA kinetics serve as a promising non-invasive biomarker for predicting clinical outcomes in advanced NSCLC treated with first-line chemoimmunotherapy or immunotherapy. These findings highlight SAA kinetics as a potential non-invasive biomarker and monitoring SAA dynamics may aid in identifying patients with higher likelihood of clinical benefit; however, prospective studies are required to determine its utility in guiding therapeutic decisions.

Keywords

• Biomarker
• Immunotherapy
• Chemoimmunotherapy
• Serum amyloid A
• Non-small cell lung cancer