Prospective validation study of nutritional and immunological predictors in immune checkpoint inhibitor efficacy for non‐small cell lung cancer

Immune checkpoint inhibitors (ICIs) have improved prognosis in non-small cell lung cancer (NSCLC). This prospective observational study aimed to validate the clinical impact of nutritional and immunological indices, including neutrophil-to-lymphocyte ratio (NLR), Glasgow prognostic score (GPS), prognostic nutritional index (PNI), controlling nutritional status (CONUT), and skeletal muscle area (SMA) in NSCLC patients treated with first-line ICIs. Three hundred and one patients with programmed cell death-ligand 1 (PD-L1) expression data were enrolled. SMA was measured using computed tomography images at the L3 level. Cut-off values were determined by our previous retrospective reports. The primary endpoint was progression-free survival (PFS). As a translational research, 15 myokines were evaluated from pre-treatment blood samples. The NLR, GPS, PNI, CONUT, and SMA were all significantly associated with PFS (p = .0128, p = .0016, p = .0046, p = .0485, and p = .0161, respectively). Multivariate analysis elucidated that age ≥75 years (p = .0256), male sex (p = .0227), combined chemotherapy (p = .0002), PD-L1 ≥50% (p = .0017), and SMA (p = .0354) were significant predictors of objective response. Multivariate analysis of PFS showed that performance status (p = .0104), PD-L1 (p <.0001), GPS (p = .0042), and SMA (p = .0367) were independent predictors. FSTL-1 was significantly lower in non-responders than in responders (p = .0212). In conclusion, the nutritional and immunological indices were validated to be significant predictors for the efficacy of ICIs. SMA was a predictor of both objective response and PFS, highlighting FSTL-1 as a potential biomarker for response to ICIs.