Abstract 2516: Influence of pre-treatment nutrition and inflammation on immunotherapy response in non-small cell lung cancer
Authors: Robinson Lary A. , Kim Youngchul , Buro Acadia , Hogue Stephanie R. , Bailey Alexis , DeNicola Gina M. , Pierce Christine , Umbarger Mark , Byrd Doratha A. 
Published: March 2024

Abstract
Purpose: Immune checkpoint inhibitor therapy (ICI) is effective in non-small-cell lung cancer (NSCLC) but only a minority respond, likely due in part to the gut microbiome. Given the coupling of host nutritional status and gut microbiota composition, we investigated the pre-treatment associations of nutritional status and biomarkers with ICI treatment response and survivals.
Methods: We recruited stage III-IV NSCLC patients. Pre-ICI treatment clinical information and blood samples were obtained. Clinician assessed ICI response and survival data were recorded. The nutritional/inflammatory indicators were compared based on treatment response and survivals. ICI Clinical Benefit was defined as 12-month progression free survival. Pearson Chi-square or Fisher’s Exact test was used to compare categorical metrics; non-parametric analysis compared continuous metrics by treatment response. Overall survivals were assessed using multivariable Cox proportional hazards models to estimate associations.
Results: Of the 76 patients recruited, all were ECOG performance status 0 (14.5%) or 1 (85.5%). 36 (47%) had Clinical Benefit with median survival 21.3 mo. vs. 6.6 mo. among the No Clinical Benefit patients (p&lt;0.01). Non-responders had significantly more often weight loss, lower serum albumin, elevated red cell distribution index (RDW) and worse scores for Frailty Index, Geriatric Nutritional Risk Index and Mini-Nutritional Assessment (MNA). Non-responders had significantly more inflammation with a higher Systemic Immune Response Index (SIRI) and RDW. Overall survival was negatively correlated with: 1. weight loss; 2. low serum albumin; 3. low serum sodium; 4. high RDW; 5. elevated total neutrophils, total white blood cells, total monocytes, neutrophil to lymphocyte ratio, and monocyte to lymphocyte ratio; 6. adverse MNA and Geriatric Nutritional Risk Index; 7. elevated SIRI and Systemic Immune Inflammation Index (SII). ICI response prediction accuracy using a solely MNA-based model was significantly high in terms of AUROC of 0.85 [95% CI= (0.76, 0.93); p&lt;0.05]. In multivariable analysis, the predictor of immunotherapy response and survival was the 6-measure MNA which strongly correlates with weight loss, low serum albumin and depressed Frailty Index.
Conclusions: An adverse nutritional status with accompanying chronic inflammation is strong predictor of non-response to ICI. Since lung cancer patients with depressed pre-treatment nutrition have a low likelihood of an ICI response, they should be promptly referred for dietician consultation for intensive nutritional therapy which may improve their clinical outlook. Considering the negative association of malnutrition/inflammation with response to ICI treatment in NSCLC patients who still qualify as ECOG performance status 0-1 patients, prospective clinical trials should also stratify their results by nutritional status.
Citation Format: Lary A. Robinson, Youngchul Kim, Acadia Buro, Stephanie R. Hogue, Alexis Bailey, Gina M. DeNicola, Christine Pierce, Mark Umbarger, Doratha A. Byrd. Influence of pre-treatment nutrition and inflammation on immunotherapy response in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2516.