Prognostic significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for advanced non-small cell lung cancer patients with high PD-L1 tumor expression receiving pembrolizumab

Ksienski, Doran; Wai, Elaine S.; Alex, Deepu; Croteau, Nicole; Freeman, A.H.; Chan, Angela; Patterson, Tiffany; Clarkson, Melissa; Fiorino, Leathia; Poonja, Zia; Fenton, David; Irons, Sarah; Lesperance, Mary

doi:10.21037/tlcr-20-541

Cited by 32 publications

(26 citation statements)

References 45 publications

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“…The results of our analysis for baseline NLR, PLR and MLR revealed the relationship between low values and better survival outcomes, confirming the aforementioned exposure. The current findings are in agreement with those reported in several previous studies (24,26,27,32,40) Similarly, the results for PLR showed that elevated values were related to poor survival (OS: HR =1.93, 95% CI: 1.51-2.01, P<0.001 and PFS: HR =1.57, 95% CI: 1.30-1.90, P<0.001). Furthermore, in a study of a large cohort (1,466 cases) of patients who underwent curative resection with stage I-IIIA NSCLC, Yuan et al (27) concluded that elevated MLR was an independent predictor for poor OS (HR =1.25, 95% CI: 1.01-1.54, P=0.035).…”

Section: Discussionsupporting

confidence: 93%

Correlation of peripheral blood biomarkers with clinical outcomes in NSCLC patients with high PD-L1 expression treated with pembrolizumab

Sánchez-Gastaldo¹,

Muñoz-Fuentes²,

Molina-Pinelo³

et al. 2021

Transl Lung Cancer Res

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Background: Immune checkpoint inhibitors (ICIs) are currently the standard therapy in advanced nonsmall cell lung cancer (NSCLC); however, there is no well-established prognostic biomarker. We investigated the relationship between survival outcomes and three peripheral blood biomarkers, including the neutrophilto-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), as well as a new score termed the risk blood biomarker (RBB), calculated from the combination of the neutrophil-monocyte-to-lymphocyte ratio (NMLR) and white blood cell count (WBC).Methods: This study included patients with stage IV or recurrent NSCLC confirmed with programmed death ligand 1 (PD-L1) expression ≥50% who received pembrolizumab monotherapy as first-line treatment at the Virgen del Rocío University Hospital in Seville, Spain. To establish the relationship between baseline peripheral blood biomarkers and survival outcomes, progression free survival (PFS) and overall survival (OS), we used the Kaplan-Meier method and multivariable Cox regression models.Results: A total of 51 patients were included in this study. In multivariate analysis, baseline NLR and PLR showed a strong association with PFS [NLR hazard ratio (HR): 0.

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Section: Discussionsupporting

confidence: 93%

Correlation of peripheral blood biomarkers with clinical outcomes in NSCLC patients with high PD-L1 expression treated with pembrolizumab

Sánchez-Gastaldo¹,

Muñoz-Fuentes²,

Molina-Pinelo³

et al. 2021

Transl Lung Cancer Res

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“…Multiple studies have shown that NLR and PLR are associated with OS in lung cancer patients treated with ICIs ( 46 – 48 ). However, the relationship between these indicators and the OS of patients with CIP is rarely reported.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Blood Biomarkers for Early Diagnosis, Severity, and Prognosis of Checkpoint Inhibitor-Related Pneumonitis in Patients With Lung Cancer

et al. 2021

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BackgroundCheckpoint inhibitor-related pneumonitis (CIP) is a potentially fatal immune-related adverse event that occurs during treatment with immune checkpoint inhibitors (ICIs). However, the roles played by peripheral blood parameters in CIP development remain unclear. Here, we aimed to identify which blood biomarkers correlated with the development and prognosis of CIP in patients with lung cancer.MethodsWe conducted a retrospective analysis of 87 patients with CIP (CIP group) and 87 patients without CIP (control group). Cytokines, blood routine, lactate dehydrogenase (LDH) and albumin (ALB) were collected at baseline (before ICIs), at onset of pneumonitis (in the CIP group), and before the last dose of ICI (in the control group). We compared the baseline values and changes over time in various blood parameters between the CIP and control groups. The CIP outcomes were collected and compared according to the median values of these parameters.ResultsSquamous carcinoma (odds ratio [OR]: 3.02; p = 0.004) and ICI monotherapy (OR: 6.56; p = 0.004) correlated with a high risk of CIP. In the CIP group, interleukin (IL)-6 and platelet-to-lymphocyte ratio (PLR) at CIP were significantly increased relative to baseline. By contrast, IL-6 and PLR reduced over time in the control group. Significant decrease in absolute lymphocyte count (ALC) and increases in IL-10, neutrophil to lymphocyte ratio (NLR), and LDH levels were observed from baseline to CIP. No significant change in these parameters was observed in the control group relative to baseline. ALB decreased in both groups, but the decrease in the CIP group was greater (9.21% vs. 2.44%; p = 0.020). High IL-6 levels (OR: 5.23, 95% confidence interval [CI]: 1.15–23.86; p = 0.033), and low levels of ALB (OR: 0.16, 95% CI: 0.04–0.64; p = 0.009) measured at the time of CIP symptom onset were associated with severe pneumonitis. Low concentration of IL-6 (hazard ratio [HR]: 0.17, 95% CI: 0.03–0.95; p = 0.044) and high ALB levels (HR: 0.28, 95% CI: 0.08–0.94; p = 0.040) were correlated with favorable overall survival in CIP.ConclusionsIncrease in IL-6, IL-10, NLR, PLR, and LDH levels or reduced ALC and ALB levels were associated with the occurrence of CIP in lung cancer patients. High IL-6 and low ALB levels at onset of CIP were related to severe grade and poor prognosis of CIP.

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“…A high neutrophil to lymphocyte ratio (NLR) in serum is known to correlate with worsened ICI clinical outcome (95)(96)(97). Although its predictive correlation with all irAEs is mostly weak, NLR distinguishes grade 3 and higher irAEs from low grade irAEs after pembrolizumab therapy and it can be used to monitor the onset of irAEs (98,99). For IMC in particular, a baseline NLR higher than 5 correlated with development of IMC (100).…”

Section: Cellular Indicatorsmentioning

confidence: 99%

Mechanisms of Immune Checkpoint Inhibitor-Mediated Colitis

et al. 2021

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Immune checkpoint inhibitors (ICIs) have provided tremendous clinical benefit in several cancer types. However, systemic activation of the immune system also leads to several immune-related adverse events. Of these, ICI-mediated colitis (IMC) occurs frequently and is the one with the highest absolute fatality. To improve current treatment strategies, it is important to understand the cellular mechanisms that induce this form of colitis. In this review, we discuss important pathways that are altered in IMC in mouse models and in human colon biopsy samples. This reveals a complex interplay between several types of immune cells and the gut microbiome. In addition to a mechanistic understanding, patients at risk should be identifiable before ICI therapy. Here we propose to focus on T-cell subsets that interact with bacteria after inducing epithelial damage. Especially, intestinal resident immune cells are of interest. This may lead to a better understanding of IMC and provides opportunities for prevention and management.

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Prognostic significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for advanced non-small cell lung cancer patients with high PD-L1 tumor expression receiving pembrolizumab

Cited by 32 publications

References 45 publications

Correlation of peripheral blood biomarkers with clinical outcomes in NSCLC patients with high PD-L1 expression treated with pembrolizumab

Correlation of peripheral blood biomarkers with clinical outcomes in NSCLC patients with high PD-L1 expression treated with pembrolizumab

Peripheral Blood Biomarkers for Early Diagnosis, Severity, and Prognosis of Checkpoint Inhibitor-Related Pneumonitis in Patients With Lung Cancer

Mechanisms of Immune Checkpoint Inhibitor-Mediated Colitis

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