Metabolic parameters by 18F-FDG PET/CT and peripheral blood biomarkers are associated with outcomes in patients with NSCLC under Immune Checkpoint Inhibitors treatment: the Immune-Metabolic-Prognostic Index (IMPI).

Objectives: The aim of this study was to identify whether metabolic parameters evaluated by 18F-FDG PET/CT and peripheral blood biomarkers were associated with clinical outcomes in patients with non-small cell lung carcinoma (NSCLC) treated with Immune Checkpoint Inhibitors (ICI). Materials and Methods: The trial was registered at http://www.clinicaltrials.gov (NCT03563482). In our prospective study, data from 33 patients (21 male, 12 female, mean age 68) with NSCLC and treated with ICI from April 2017 to December 2018 were collected. Complete blood cell counts before and after 8 weeks of treatment were measured. All patients underwent 18F-FDG PET/CT both at baseline and at 8 weeks after the start of ICI. Progression-free survival (PFS) and overall survival (OS) were determined and compared using the Kaplan-Meier method and the log-rank test. The prognostic values of each variable were evaluated with univariate Cox proportional hazard regression analysis. The median follow-up was 11.3 months (range 1-17 months).

Results: Among the variables selected by univariate analysis, a low post-treatment neutrophil-to-lymphocyte ratio (post-NLR < 4.9) and low post-TLG (< 541.5 ml) were significantly and independently associated with both better PFS (HR 0.273; 95%CI, 0.92-0.806 and HR, 0.295; 95%CI, 0.092-0.806, respectively) and better OS (HR 0.044; 95%CI, 0.007-0.275 and HR, 0.204; 95%CI, 0.042-0.988, respectively) in multivariate analysis. Afterwards, an immune-metabolic prognostic index (IMPI), based on post-NLR lower than 4.9 and post-TLG lower than 541.5 ml was developed, categorizing 3 groups: high risk, 2 factors; intermediate risk, 1 factor; low risk, 0 factors. Median PFS for low, intermediate and high risk was 7.8 months (95%CI, 4.6-11.0), 5.6 months (95%CI, 3.8-7.4), and 1.8 months (95%CI, 1.6-2.0) (p<0.001) respectively. Likewise, median OS was 15.2 months (95%CI, 10.9-19.6), 13.2 months (95%CI, 5.9-20.3), and 2.8 months (95%CI, 1.4-4.2) (p<0.001), respectively (Figure 1).

Conclusions: IMPI at 8 weeks after ICI initiation, combining both immune (post-NLR < 4.9) and metabolic (post-TLG < 541.5) biomarkers, was correlated with longer PFS and OS. This result suggests that IMPI can be a potentially valuable tool for identifying NSCLC patients who likely benefit from treatment with ICI, although further larger studies are warranted to establish IMPI as predictor of outcome. The Italian Association for Research on Cancer (AIRC - Associazione Italiana per la Ricerca sul Cancro) is acknowledged for the support on research.

• Download figure
• Open in new tab
• Download powerpoint