Peripheral blood biomarkers predict immune-related adverse events in non-small cell lung cancer patients treated with pembrolizumab: a multicenter retrospective study

Abstract

Background: Pembrolizumab is currently the standard treatment for patients with advanced non-small cell lung cancer (NSCLC). However, the association between immune-related adverse events (irAEs) and peripheral blood cell counts remains unclear. We aimed at identifying peripheral blood cell counts that may predict the development of pembrolizumab-induced irAEs. Methods: We retrospectively analyzed data on consecutive patients with advanced NSCLC who received pembrolizumab monotherapy as first-line or later-line therapy at the National Cancer Center Hospital and Keio University Hospital. We used data between December 2015 and November 2018. The primary endpoint was the relationship between peripheral blood cell count data and early-onset irAEs during the 6-weeks study period. Receiver operating characteristic (ROC) curve and multivariable logistic regression analyses were performed. Results: In total, 92 patients were evaluated, of whom 45 (48.9%) had at least one irAE during the first 6-weeks after treatment initiation. The ROC curves revealed that the optimal cutoff of pretreatment absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) for onset of irAEs were 1459, 2.320, 1.538, and 165, respectively. Multivariable logistic regression analyses revealed that pretreatment ALC>1450 and LMR>1.6 were significantly associated with a reduced risk for onset of any irAEs, whereas pretreatment NLR>2.3 and PLR>165 were significantly associated with an increased risk. Conclusions: The findings suggest that considering the routine availability of blood cell count data before the initiation of treatment with pembrolizumab, it may be useful in identifying early-onset irAEs during the 6-weeks study period in clinical practice.

Predictive Factors Correlated with the Development of Immune-Related Adverse Events in Patients with Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors

“…Egami et al reported that markers, such as NLR, PLR, absolute lymphocyte count, and lymphocyte-to-monocyte ratio, were useful predictors associated with the development of irAEs by setting an optimal cutoff value using the receiver operating characteristic curve. 11 Optimal cutoff values for these markers vary depending on the target patient population and should be interpreted with caution.…”

“…Egami et al reported that pretreatment NLR > 2.3 and PLR > 165 were significantly correlated with an increasing incidence of irAEs in NSCLC patients who received pembrolizumab monotherapy. 11 Another retrospective study reported that elevated body mass index, higher number of pembrolizumab cycles, and derived NLR < 3 were correlated with an increased incidence of irAEs in patients receiving pembrolizumab for various cancers, such as lung cancer, melanoma, lymphoma, gastric cancer, and urothelial cancer. 12 Although these studies have reported on predictive factors correlated with the development of irAEs in clinical practice, patients in these studies only received pembrolizumab; other ICIs have not been investigated.…”

Prognostic Value of Baseline Medications Plus Neutrophil-to-Lymphocyte Ratio in the Effectiveness of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer: A Retrospective Study

“…This single-center, retrospective observational study was carried out at the National Cancer Center Hospital, a high-volume cancer center in Tokyo, Japan, using data retrieved from electronic medical records. The methodology adopted in this observational study adhered to the STROBE Statement (23) and was the same as that followed in previous studies conducted by our coauthors (24)(25)(26).…”

The Efficacy and Safety of Fruquintinib Plus PD-1 Inhibitor in ≥3 line MSS Metastatic Colorectal Cancer Patients

“…It was verified that mOS in NLR ≥ 3.06 group was shorter than in NLR<3.06 group (2.7m vs 8.6m P=0.000). Higher NLR was significantly associated with an increased risk of immune-related adverse events (irAE) [24]. In our research, the NLR values of patients who experienced immune-related encephalitis and cardiotoxicity were 12.5 and 10.7 respectively, obviously higher than the cutoff value.…”