Dissecting the impact of Controlling Nutritional Status (CONUT) score on survival outcomes and immune-inflammatory profiles in patients with advanced NSCLC undergoing first-line immunotherapy

Background: The immunonutritional background has been deeply implicated in cancer behavior and clinical outcomes. In this study, we explored the prognostic impact of the Controlling Nutritional Status (CONUT) score through its correlation with blood immunophenotypes and cytokines to provide an easily available non-invasive tool to predict the survival benefit from first-line immune checkpoint inhibitors±chemotherapy (ICI±CHT) in patients affected by advanced non-small cell lung cancer (aNSCLC). Material and methods: From a prospective cohort of patients with aNSCLC treated with first-line ICI±CHT, clinicopathological data and baseline blood samples for the assessment of CONUT score (albumin, lymphocytes, total cholesterol), relevant immunophenotypes (flow cytometry) and cytokines (multiplex array) were collected. Correlations of CONUT score with survival outcomes (progression-free/overall survival [PFS/OS]) and circulating immune-inflammatory benchmarks were analyzed. Results: Among 178 patients enrolled in the AIRC (Italian Association for Cancer Research) project, 153 received ICI±CHT as first-line. Nutritional status tested by CONUT score was available in 137 cases and was <3, meaning good nutritional status, in 77 (56.2%), whereas scored ≥3 in 60 (43.8%), meaning an impaired nutritional status. At a median follow-up of 27.4 months (95% CI 22.9 to 32.0), patients with a CONUT score <3, compared to those with CONUT score ≥3, experienced significantly longer PFS (median PFS 8.03 vs 3.88 months, HR 0.58, 95% CI 0.40 to 0.84, p=0.004) and OS (median OS 22.24 vs 8.75 months, HR 0.61, 95% CI 0.40 to 0.94, p=0.03). The multivariable analysis, adjusting for age, histology, metastatic sites, sex, programmed death-ligand 1 (PD-L1), Eastern Cooperative Oncology Group Performance Status and treatment type, confirmed the prognostic impact of CONUT score in terms of PFS (HR 0.61, 95% CI 0.41 to 0.93, p=0.02) and OS (HR 0.60, 95% CI 0.38 to 0.96 p=0.03). Patients with CONUT score ≥3 displayed significantly higher blood levels of interleukin (IL)-1β, IL-12, IL-10, interferon-γ, IL-6, and soluble PD-L1 compared with those with CONUT score <3. A higher fraction of CD14+ cells (p=0.01) and CD8+Ki67+ (p<0.001) lymphocytes also characterized the blood of patients with CONUT score ≥3 compared with those with CONUT score <3. Conclusion: A baseline good nutritional status (CONUT score <3) is associated with a distinct circulating immune-inflammatory profile and correlates with improved clinical outcomes in patients with aNSCLC treated with first-line ICI±CHT.