Nutritional status associates with immunotherapy clinical outcomes in recurrent or metastatic head and neck squamous cell carcinoma patients

Background: Beyond programmed death-ligand 1 (PD-L1) assessed by the combined positive score (CPS) and tumor mutational burden (TMB), no other biomarkers are approved for immunotherapy interventions. Here, we investigated whether additional clinical and pathological variables may impact on immunotherapy outcomes in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients.Methods: R/M HNSCC patients treated with immunotherapy were reviewed. Analyzed variables at baseline included: clinicopathological, laboratory, and variables reflecting the host nutritional status such as the prog-nostic nutritional index (PNI) and albumin. The primary endpoint was progression free survival (PFS). The secondary endpoints were overall survival (OS) and objective response rate (ORR). Univariable and multivari-able Cox models were fitted and random forest algorithm was used to estimate the importance of each prognostic variable.Results: A total of 100 patients were treated with immunotherapy; 50% with single agent and 50% with experimental immunotherapy combinations. In the multivariable analysis, both ECOG performance status (HR: 1.73; 95%CI 1.07-2.82; p = 0.03) and PNI levels (10-point increments, HR: 0.66; 0.46-0.95; p = 0.03) were significantly associated with PFS. However, the derived neutrophil to lymphocyte ratio (dNLR) and lactate de-hydrogenase (LDH) were not significantly associated with PFS (p-values > 0.15). In the OS analysis, albumin and PNI were the only statistically significant factors in the multivariable model (p < 0.001).Conclusions: In our cohort, PNI and ECOG performance status were most strongly associated with PFS in R/M HNSCC patients treated with immunotherapy. These results suggest that parameters informative of nutritional status should be considered before immunotherapy.