Obesity, dyslipidemia, and diabetes as determinants of response to immune checkpoint inhibitors in non-small cell lung cancer

e21104 Background: Immune checkpoint inhibitors (ICI) are standard of care in the treatment of non-small cell lung cancer (NSCLC). Predictive markers of response to ICI are being studied extensively. Obesity has been correlated with a better response to ICI in NSCLC and other types of cancer. This may in-part be related to high circulating leptin or impaired T-cell fatty acid oxidation within the tumor microenvironment. We aim to further explore the effects of obesity, dyslipidemia and other components of the metabolic syndrome such as diabetes on treatment outcomes on NSCLC patients receiving ICI. Methods: We conducted a retrospective cohort study in patients with NSCLC treated with pembrolizumab, nivolumab, durvalumab, cemiplimab or atezolizumab as monotherapy or combined with chemotherapy at Mount Auburn and Lahey Hospital between January 2016 to June 2021. Obesity was defined as body mass index (BMI) > 30 kg/m2, dyslipidemia and type 2 diabetes were defined by ICD-10 diagnosis codes. Overall survival was evaluated. Kaplan-Meier survival analysis and cox proportional hazards regression were used to assess correlation between overall survival and obesity, dyslipidemia, type 2 diabetes, metformin use and statin use. These were adjusted for age, biological sex, cancer stage, ECOG and smoking status. Patients with BMI < 18.5 were excluded. Results: We identified 408 patients with NSCLC who were treated with ICIs. Of these, 66.7% had adenocarcinoma, 29.1% had squamous and 4.2% had either adenosquamous, large cell or poorly differentiated carcinoma. Among these patients 23.3% were classified as obese, 55.6% had dyslipidemia and 23% had type 2 diabetes. Of these, 66% of patients received ICIs as monotherapy. Median survival was 840 days in obese patients compared to 483 days in non-obese patients (HR 0.66, CI 0.42-0.92, p = 0.014). Conversely, within this cohort, median survival in patients with dyslipidemia was 483 days when compared to 762 days in controls (HR 1.37, CI 1.07-1.81, p = 0.013). Overall survival was not significantly different between type 2 diabetes, metformin use or statin use. Conclusions: Our study shows a trend towards a better survival in obesity and poor survival associated with dyslipidemia. Obesity and dyslipidemia may be important markers of ICI response in patients with NSCLC regardless of treatment strategies. Further studies are needed to explore the molecular mediators within the metabolic syndrome that may provide a synergistic effect with immune checkpoint inhibitors.