Background: The dual roles of inflammation in malignancy has been well-described. Neutrophils play a key role in inflammation and carcinogenesis. We previously showed that high NLR may confer resistance to PD1/PDL1 inhibitors in lung cancer patients. In addition, obesity has been shown to produce chronic inflammation and neutrophil dysfunction have been described. The interplay between obesity and neutrophil in solid tumor patients treated with immunotherapy is unknown. Methods: We retrospectively evaluated 408 patients with solid tumors who treated with immunotherapies at the University of Miami. Cox regression was performed to evaluate correlation of obesity (BMI >30) and NLR <5 with Progression Free Survival (PFS) and Overall Survival (OS). Pearson Correlation was used for correlation between BMI and NLR. Results: Median follow-up was 8.6 months. There were head, neck and thoracic (n=257), gastrointestinal (n=32), genitourinary (n=58), skin and musculoskeletal (n=61). There were 230 males, mean age was 65.8. Treatments include nivolumab (n=204), pembrolizumab (n=128), atezolizumab (n=35), and combination with ipilimumab (n=41). There were underweight (BMI<18.5, n=27), normal weight (18.5≤BMI<25, n=186), overweight (25≤BMI<30, n=117), and obese patients (BMI≥30, n=78). Obesity (BMI≥30) and NLR <5 were strongly correlated with better OS with HR: 3.031 and HR: 2.424, respectively. (Table 1) There was trend of better PFS in obese patients, however it was not statistically significant. BMI and NLR showed inverse correlation. (r= -0.172, p=0.001) Conclusions: Surrogates of inflammation, such as obesity and NLR in patients with solid cancer may predict immunotherapy responses. High NLR was associated with adverse clinical outcomes and failure to checkpoint inhibitors, perhaps due to unfavorable tumor-associated neutrophil phenotypes. There was also a strong correlation between obesity and overall survival in these solid tumor patients.

Table 1. Multivariate analysis

 PFS OS 
Factor HR 95% C.I. p-value HR 95% C.I. p-value 
ECOG>1 2.188 (1.561-3.068) 0.0001 3.031 (1.937-4.742) 0.0001 
BMI<30 1.136 (0.806-1.601) 0.468 2.934 (1.484-5.801) 0.002 
NLR≥5 1.704 (1.301-2.230) 0.0001 2.424 (1.661-3.538) 0.0001 
 PFS OS 
Factor HR 95% C.I. p-value HR 95% C.I. p-value 
ECOG>1 2.188 (1.561-3.068) 0.0001 3.031 (1.937-4.742) 0.0001 
BMI<30 1.136 (0.806-1.601) 0.468 2.934 (1.484-5.801) 0.002 
NLR≥5 1.704 (1.301-2.230) 0.0001 2.424 (1.661-3.538) 0.0001 
View Large

Citation Format: Wungki Park, Vaia Florou, Alfredo Torres, Diana Saravia, Sandra Algaze, Gilberto Lopes, University of Miami. An inflammation paradox: Obesity vs. neutrophil-lymphocyte ratio in immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 701.

©2018 American Association for Cancer Research.
2018
American Association for Cancer Research.