Dynamics of Neutrophils-to-Lymphocyte Ratio Predict Outcomes of PD-1/PD-L1 Blockade

Moschetta, Michele; Uccello, Mario; Kasenda, Benjamin; Mak, Gabriel; McClelland, Anissa; Boussios, Stergios; Förster, Martin; Arkenau, Hendrik Tobias

doi:10.1155/2017/1506824

Cited by 59 publications

(50 citation statements)

References 21 publications

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“…Zaragoza et al [ 21 ] also found that an ANC:ALC ratio of 4 or higher in melanoma patients treated with ipilimumab was associated with worse OS in univariate and multivariate analysis, and remained as an independent prognostic factor (HR, 2.2; 95% CI, 1.01–4.78). Moschetta et al [ 22 ] described a negative effect on PFS after 2 cycles of anti-PD-1/anti-PD-L1 in various solid tumor patients (including NSCLC) with a baseline elevated neutrophil to lymphocyte ratio of 3.4. Furthermore, our findings are similar to smaller studies in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

“…For example, a reference of 5.0 for ANC:ALC has been used in the melanoma literature. Different cutoff points for ANL:ALC have been used in other recent NSCLC studies [ 22 , 24 , 25 ]. The reason for this variation is likely attributed to the baseline difference in patient population, timing of ANC:ALC in relation to the treatment and statistical methods.…”

Section: Discussionmentioning

confidence: 99%

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

Soyano¹,

Dholaria²,

Marin-Acevedo³

et al. 2018

j. immunotherapy cancer

109

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Soyano¹,

Dholaria²,

Marin-Acevedo³

et al. 2018

j. immunotherapy cancer

109

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“…We excluded all patients who received only part of treatment at our center and patients who were on steroids before obtaining a complete blood count (CBC). Using steroids was expected to confound the results of the study as it leads to leukocytosis and specifically neutrophilia [16,17].…”

Section: Initial Step In Data Collection From the Electronic Medical mentioning

confidence: 99%

“…In patients with different types of malignant tumors, NLR correlates with the extent of therapeutic success in response to chemotherapy and immunotherapy [13][14][15][16][17]. Moreover, other blood-based markers i.e.…”

Section: Plos Onementioning

confidence: 99%

The clinical value of peripheral immune cell counts in pancreatic cancer

Abu-Shawer

Shurman

et al. 2020

PLoS ONE

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Background Elevated neutrophil-lymphocyte ratio (NLR) is linked to poor overall survival (OS) in pancreatic cancer. We aim to investigate the association of the various hematologic markers, in particular NLR among others, with distant metastases, a common feature in pancreatic cancer. Methods Clinical data from 355 pancreatic cancer patients managed at King Hussein Cancer Center (Amman-Jordan) have been reviewed. We examined the relationship between absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophilic count (AEC), absolute monocytic count (AMC), NLR, monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR) with the presence of baseline distant metastases and OS. Receiver Operating Characteristic (ROC) curve analysis was plotted to identify the NLR optimum cutoff value indicative of its association with distant metastases. Results On univariate and multivariate analyses patients whom on presentation had high NLR (�3.3) showed more baseline distant metastases compared to patients with low NLR (<3.3), (p-value: <0.0001 and <0.0001, respectively). Patients with high baseline ANC (�5500/μL), AMC (�600/μL), MLR (�0.3) had more baseline distant metastases in comparison to patients with lower values (p-value: 0.

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“…It has also been shown that, besides baseline values, lymphocyte variation during treatment could also predict ICI activity and patients' outcome [17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

ROC Analysis Identifies Baseline and Dynamic NLR and dNLR Cut-Offs to Predict ICI Outcome in 402 Advanced NSCLC Patients

Carnio

Mariniello

Pizzutilo

et al. 2020

JMP

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Background: Neutrophil-to-Lymphocyte Ratio (NLR) and derived Neutrophils-to-(Leukocytes minus neutrophils) Ratio (dNLR) have been proposed as possible biomarkers of response to immune checkpoint inhibitors (ICI). However, in non-small cell lung cancer (NSCLC) studies, various NLR and/or dNLR cut-offs have been used, manly based on previous reports on melanoma. Methods: In this Italian multicenter retrospective study, NLR, dNLR, platelet-to-lymphocyte ratio, albumin, and lactate dehydrogenase (LDH) were longitudinally assessed in patients with stage IV non-small cell lung cancer (NSCLC) treated with ICI. The primary objective was to evaluate if baseline parameters predicted response to ICI, using Receiver Operating Characteristic (ROC) curves. Secondary endpoint was to evaluate if dynamic changing of NLR and dNLR also predicted response. Results: Data of 402 patients were collected and analyzed. Among the baseline parameters considered, NLR and dNLR were the most appropriate biomarkers according to the ROC analyses, which also identified meaningful cut-offs (NLR = 2.46; dNLR = 1.61). Patients with low ratios reported a significantly improved outcome, in terms of overall survival (p = 0.0003 for NLR; p = 0.0002 for dNLR) and progression free survival (p = 0.0004 for NLR; p = 0.005 for dNLR). The role of NLR and dNLR as independent biomarkers of response was confirmed in the Cox regression model. When assessing NLR and dNLR dynamics from baseline to cycle 3, a decrease ≥1.04 for NLR and ≥0.41 for dNLR also predicted response. Conclusions in our cohort, we confirmed that NLR and dNLR, easily assessable on peripheral blood, can predict response at baseline and early after ICI initiation. For both baseline and dynamic assessment, we identified clinically meaningful cut-offs, using ROC curves.

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Dynamics of Neutrophils-to-Lymphocyte Ratio Predict Outcomes of PD-1/PD-L1 Blockade

Cited by 59 publications

References 21 publications

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

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

The clinical value of peripheral immune cell counts in pancreatic cancer

ROC Analysis Identifies Baseline and Dynamic NLR and dNLR Cut-Offs to Predict ICI Outcome in 402 Advanced NSCLC Patients

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