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

Abstract

BackgroundAnti-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 methodsWe 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.ResultsWe 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.ConclusionsIncreased 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.Electronic supplementary materialThe online version of this article (10.1186/s40425-018-0447-2) contains supplementary material, which is available to authorized users.

Overexpression of B7H5/CD28H is associated with worse survival in human gastric cancer

“…5 PD-L1/PD-1 has become a hot area of research in recently years. 6,7 The B7/CD28 family regulates the proliferation and function of T cells as antigen-presenting cells (APCs). In addition, some tumours can evade immune elimination, because of overexpression of PD-L1/PD-1.…”

“…(range:[1][2][3][4][5][6][7][8][9][10][11][12]. The median score was used to determine the cut-off value of low or high CD28H expression.…”

Current status of prognostic factors in patients with metastatic renal cell carcinoma

“…Although there are few reports of prognostic factors for mRCC treated with ICIs, several studies have shown the association of some inflammatory markers with the prognosis of patients with various malignant diseases treated with ICIs (Table 3). [97][98][99][100][101][102][103][104][105][106] These reports indicate that the parameters related to inflammation might also have some prognostic impact on patients with mRCC treated with ICIs. Further study is expected to clarify the link between the mechanism of inflammation and the effects of ICIs, and to identify the markers related to inflammation to predict or evaluate the effects of ICIs.…”

“…Although there are few reports of prognostic factors for mRCC treated with ICIs, several studies have shown the association of some inflammatory markers with the prognosis of patients with various malignant diseases treated with ICIs (Table ) . These reports indicate that the parameters related to inflammation might also have some prognostic impact on patients with mRCC treated with ICIs.…”

Possibilities of Improving the Clinical Value of Immune Checkpoint Inhibitor Therapies in Cancer Care by Optimizing Patient Selection

“…Other widely acknowledged prognostic markers for deleterious systemic inflammation include an elevated neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH). NLR is a marker for the general immune response to various stress stimuli, and it is shown to predict outcome among NSCLC and melanoma patients treated with PD-1 inhibitors [78,[81][82][83][84], and CTLA-4 antibodies [78,83,85,86]. Raised LDH level is a classic inflammatory marker in patients with cancer.…”