Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies

Abstract

Background: Anti-programmed cell death 1 (PD-1) antibodies have demonstrated improved overall survival (OS) and progression-free survival (PFS) in a subset of patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). To date, no blood biomarkers have been identified in NSCLC to predict clinical outcomes of treatment with anti-PD-1 antibodies.

Patient and methods: We performed an analysis of retrospectively registered data of 157 patients with advanced NSCLC treated with anti-PD-1 antibodies at Mayo Clinic in Florida and Rochester. White blood cell count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), ANC to ALC (ANC: ALC) ratio, absolute eosinophil count, absolute monocyte count (AMC), platelet counts, and myeloid to lymphoid (M:L) ratio at baseline and throughout treatment were assessed. Kaplan-Meier method and Cox proportional hazards model were performed.

Results: We treated 146 patients with nivolumab and 11 with pembrolizumab between January 1, 2015 and April 15, 2017. At median follow-up of 20 months, median OS and PFS were 6.0 and 2.6 months, respectively. Higher baseline ANC, AMC, ANC: ALC ratio and M: L ratio correlated with worse clinical outcomes in patients who underwent anti-PD-1 treatment. A baseline ANC: ALC ratio of 5.9 or higher had a significantly increased risk of death (hazard ratio [HR] =1.94; 95% confidence interval [CI], 1.24-3.03; P = 0.004) and disease progression (HR, 1.65; 95% CI, 1.17-2.34; P = 0.005) compared with patients with lower ratio. Similarly, a baseline M: L ratio of 11.3 or higher had significantly increased risk of death (HR, 2.5; 95% CI, 1.54-4.05; P < 0.001), even after a multivariate analysis (HR, 2.31; P = 0.002), compared to those with lower ratio.

Conclusions: Increased baseline ANC: ALC ratio and M: L ratio before initiation of anti-PD1 antibodies were associated with poor PFS and OS in advanced NSCLC patients. The potential predictive value of these readily available biomarkers might help with risk stratification and treatment strategies. These findings warrant further investigation in a larger, prospective study.

Keywords: Anti-PD-1; Immunotherapy; Nivolumab; Non-small cell lung cancer; Pembrolizumab; Relapse/progression.

Fig. 1

Kaplan-Meier Survival Curves for Overall Survival (OS; a, c, e, g) and Progression-Free Survival (PFS; b, d, f, h) of Non-Small Cell Lung Cancer Patients Treated With Anti-PD-1 Antibodies. Time is represented in months from start date of immunotherapy. a and b, patients are stratified by absolute neutrophil to lymphocyte (ANC:ALC) ratio. Blue lines represent ANC:ALC ratio < 5.9 and red lines, ANC:ALC ratio ≥ 5.9. c and d, patients are stratified by myeloid to lymphoid (M:L) ratio. Blue lines represent M:L ratio < 11.3 and red lines, M:L ratio ≥ 11.3. e and f, patients are stratified by absolute monocyte count (AMC). Blue lines represent AMC < 0.63 × 10⁹/L and red lines, AMC ≥ 0.63 × 10⁹/L. g and h, patients are stratified by absolute neutrophil count (ANC). Blue lines represent ANC < 7.5 × 10⁹/L and red lines, ANC ≥ 7.5 × 10⁹/L