Lymphocyte-to-Monocyte Ratio Is a Predictive Biomarker of Response to Treatment with Nivolumab for Gastric Cancer

Abstract

<b><i>Introduction:</i></b> Patients with unresectable or recurrent gastric cancer who have an objective response (OR) to nivolumab monotherapy are expected to have a good long-term prognosis. However, the OR rate for nivolumab treatment is low at 11%, and there is a need for biomarkers to predict the treatment response. This study aimed to analyze the significance of systemic inflammation-related variables and clinicopathologic characteristics as predictive markers of response to nivolumab monotherapy in patients with advanced gastric cancer. <b><i>Methods:</i></b> In this retrospective cohort study, we enrolled 71 consecutive patients who received nivolumab monotherapy for unresectable or recurrent gastric cancer. Receiver operating characteristic curve analysis was performed to determine the cutoff values of systemic inflammation-related variables, predictors of treatment response, and other prognostic factors related to nivolumab therapy. We focused on systemic inflammation-related variables measured before nivolumab induction and 2 weeks after its first administration and performed multivariate analysis to assess whether they could be used as prognostic factors. <b><i>Results:</i></b> Multivariate analysis revealed that a lymphocyte-to-monocyte ratio (LMR) of ≤3.28 after 2 weeks of initial nivolumab treatment (2wLMR) is a statistically significant predictor of treatment response (<i>p</i> = 0.012). The progression-free survival (PFS) rate of patients with liver metastasis was significantly worse than that of the other patients (1-year PFS: 0.0 vs. 24.4%, respectively; <i>p</i> = 0.005). The overall survival (OS) of patients with a low 2wLMR was significantly longer than that in patients with a high 2wLMR (1-year OS: 37.4 vs. 18.9%, respectively; <i>p</i> = 0.022). <b><i>Conclusions:</i></b> Thus, the 2wLMR could be a useful biomarker to predict response to nivolumab treatment and the prognosis of unresectable and recurrent gastric cancer.

Prognostic value of inflammation‐related biomarkers in patients with gastroenteropancreatic neuroendocrine neoplasms: A systematic review and meta‐analysis

“…35 Notably, LMR has shown predictive potential for immune checkpoint inhibitor effectiveness in various cancer types, including melanoma, non-small cell lung cancer, and gastric cancer. [50][51][52] Though we did not observe any association between the LMR and OS or PFS, we still believe LMRs to be valuable research directions.…”

“…Therefore, lower LMR may reflect weaker regional immunity and the presence of an inflammatory state, promoting tumor growth within the microenvironment 35 . Notably, LMR has shown predictive potential for immune checkpoint inhibitor effectiveness in various cancer types, including melanoma, non‐small cell lung cancer, and gastric cancer 50–52 . Though we did not observe any association between the LMR and OS or PFS, we still believe LMRs to be valuable research directions.…”

Exploratory Analysis of Patients With Gastric/Gastroesophageal Junction Adenocarcinoma With or Without Liver Metastasis From the Phase 3 RAINBOW Study

“…In a multicenter study involving 200 patients treated with third-line nivolumab, the presence of LM was prognostic for PFS in both univariate (HR, 1.55; 95% CI, 1.12–2.14; P=0.008) and multivariate (HR, 2.01; 95% CI, 1.40–2.89; P<0.001) analyses. Similarly, Tokumaru et al [ 29 ] observed significantly worse PFS rates among patients with LM treated with nivolumab than among other patients (1-year PFS: 0.0 vs. 24.4%, respectively; P=0.005). The results obtained in our study are inconsistent with published data for OS, and our data showed that the presence of LM was not prognostic for OS (HR, 1.13; 95% CI, 0.95–1.35; P=0.1575), but it was for PFS (HR, 1.36; 95% CI, 1.15–1.61; P=0.0003).…”

Prognostic value of lymphocyte-to-monocyte ratio in gastric cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

“…Notably, two of the eligible articles ( 19 , 20 ) included two cohort studies respectively, resulting in a total of eight cohort studies. Among them, seven cohort studies were retrospective ( 19 , 20 , 24 , 26 , 27 ), whereas the remaining one was prospective ( 25 ). All cohort studies were published in English and released between 2021 and 2022.…”