The distinct prognostic impact of circulating lipid profile according to neutrophil to lymphocyte ratio in patients with advanced solid tumors treated with immune check point inhibitors.

Background: Immune checkpoint inhibitors (ICIs) revamped the treatment landscape of several advanced solid tumors. The components of lipid profile may influence immune cells phenotype and activity, thus potentially impact on clinical benefit from ICIs. Moreover, neutrophil-to-lymphocyte ratio (NLR) is known to be a prognostic factor in cancer patients (pts). This study aims to investigate the different impact of each component of lipid profile in pts with advanced cancer treated with ICIs according to NLR value. Methods: We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile [total cholesterol (TC), triglycerides (TGs), low-density lipoproteins (LDL), high-density lipoproteins (HDL)] of consecutive advanced solid cancer pts treated with ICIs and we investigated their impact on progression free survival (PFS) and overall survival (OS) in the whole cohort and also in pts with NLR < 4 and NLR ⩾ 4. Results: Among 407 pts enrolled, 65% (N=267) were men, 52% (N=225) had non-small cell lung cancer, 77% (N=316) were treated with ICIs as monotherapy. In the overall population, pts with TC ⩾ 200 mg/dl showed longer PFS (8.1 vs 5.4 months, p=0.2), although not reaching statistical significance, and significantly longer OS (19.4 vs 11.7 months, p=0.04) compared to TC<200 mg/dl. Conversely, pts with TG ⩾ 150 mg/dl detained shorter PFS (4.1 vs 6.6 months, p=0.006) and OS (11.3 versus 14.2 months, p=0.03) compared to TG<150 mg/dl. Their prognostic value was maintained in multivariable analysis for OS. Considering NLR < 4 subgroup (N=196), pts with TG < 150 mg/dl and LDL < 100 mg/dl showed better PFS (12.7 versus 5.1 months, p=0.01 and 18.8 vs 5.7 months, p=0.004, respectively) and OS (20.4 vs 12.6 months, p=0.02 and 33.2 versus 13.8 months, p=0.007) compared to pts with TG ⩾ 150 mg/dl and LDL ⩾ 100 mg/dl. Considering NLR ⩾ 4 subgroup, pts with TC ⩾ 200 mg/dl experienced longer PFS (8.1 vs 2.7 months, p=0.008) and OS (15.5 vs 3.7 months, p=0.004) compared to TC<200 mg/dl; in addition males with HDL ⩾ 40 mg/dl and females with HDL ⩾ 50 mg/dl showed significantly longer PFS (5.9 vs 3.7 months, p=0.002), and numerically longer OS (9.9 vs 6.2 months, p=0.09). Conclusions: Each component of circulating lipid profile seems to have distinct prognostic impact according to NLR subgroup, highlighted the complex interaction between immune-inflammatory status and lipid metabolism.