Influence of Pre-Treatment Nutrition and Inflammation on Immunotherapy Response in Non-Small Cell Lung Cancer

Background/Objectives: Immune checkpoint inhibitor therapy(ICI) offers advanced-stage, non-small-cell lung cancer(NSCLC) patients effective treatment. However, only a minority of patients respond. Prior studies suggested gut microbiota are involved in immunotherapy response. Nutritional status significantly interacts with the gut microbiota. We investigated associations of pre-treatment nutrition- and inflammation-related indicators with immunotherapy response in NSCLC. Methods: We recruited 76 treatment-naïve stage III-IV NSCLC patients. Pre-ICI-treatment clinical information and blood samples were obtained. Clinician-assessed immunotherapeutic response defined clinical benefit from immunotherapy as 12-month progression-free-survival. We estimated associations of nutritional and inflammatory indicators with treatment response and survival using multivariable logistic regression and Cox proportional hazards regression analyses. Results: Approximately 47% of the study population had a clinical benefit with an overall median survival of 21.3 months compared to 6.6 months among no clinical benefit patients(p< 0.01). Those with no clinical benefit lost significantly more weight and skeletal muscle, and had lower serum albumin, Frailty Index, Geriatric Nutritional Risk Index, and Mini-Nutritional Assessment(MNA) scores. They also had higher systemic inflammation as reflected by elevated red blood cell distribution width(RDW) and Systemic Immune Response Index(SIRI). Key nutritional and inflammatory indicators were also associated with overall survival. Multivariable analyses highlighted MNA as the strongest predictor of immunotherapy response and overall survival, which is much better than the lauded PD-L-1 score. Conclusions: Adverse nutritional status and inflammation strongly predict non-response to immunotherapy and post-treatment survival. Since NSCLC patients with depressed pre-treatment nutrition and inflammation have a low probability of ICI response, they will likely benefit from intensive nutritional intervention.