Association of baseline higher platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios with less durable radiographic response to immune checkpoint inhibitors in non-small cell lung cancer.
Authors: Cao Yenong , Palmer John P. , Ibrahim Samer , Dhawan Natasha , Afzal Muhammad Zubair , Shirai Keisuke 
Published: June 2021

e21137

Background: Immune checkpoint inhibitors (ICI) are the standard of care in the treatment of non-small cell lung cancer (NSCLC). ICIs are commonly used in combination with chemotherapy but may be used as monotherapy in selected cases. Registration trials have shown a response rate of 40–50% in such patients and a durable response in some patients. However, there are no reliable predictive markers that determines the response and its durability. Recruitment of the inflammatory cells in the tumor microenvironment (TME) can determine the response to ICIs and an increased inflammatory state can be a poor prognostic factor. Peripheral inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) can reflect the inflammatory changes within the TME. We aim to study the effect of high NLR and PLR on the radiographic response and its durability in NSCLC patients treated with ICIs. Methods: We conducted a retrospective analysis on 178 NSCLC patients treated with ICIs such as pembrolizumab, nivolumab, ipilimumab/nivolumab or atezolizumab either alone or in combination with chemotherapy. Radiographic response, and the duration of radiographic response (date of best response to radiographic progression), NLR, and PLR were calculated at baseline and 8 weeks since the start of ICI. High NLR and PLR was defined as greater than the median NLR and PLR values. Cox regression univariate and multivariate analyses were performed. Logistic regression and Chi-square tests were applied. Results: Overall 81% patients had adenocarcinoma and 19% patients had squamous, adenosquamous or large cell carcinoma. Majority of the patients were female (56.2% vs. 43.8%). The objective response rate (ORR) was 45.1% and the disease control rate (DCR) was 75.8%. The ORR was 51% in patients receiving ICI as first line therapy compared to 35% in patients who received ICI as a second line therapy. There was statistically significant difference in median duration of response in patients with high vs. low NLR (9.8 months vs. 18 months, P = 0.01, 95% CI 10.9– 26.2) and high vs. low PLR (9.0 months vs. 17 months, P = 0.03 95% CI 10.9–24.33) at baseline. The baseline odds ratio (OR) of response in the high NLR and high PLR group was 0.73 (P = 0.5, 95% CI 0.36–1.64) and 0.63 (P = 0.2, 95% CI 0.32–1.23), respectively. However, the odds to respond to ICI decreased significantly in patients with high NLR and PLR at 8 weeks [NLR (OR = 0.16, P = 0.0001, 95% CI 0.06–0.43)] and [PLR (OR = 0.27, P = 0.005, 95% CI 0.1–0.6). Conclusions: NLR and PLR may be reliable surrogate markers determining the durability of response to ICI in NSCLC patients. Standard imaging studies and serial monitoring may be beneficial to monitor the response to ICIs. However, prospective studies are needed to develop predictive and prognostic models utilizing these indices.