Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced or recurrent non-small cell lung cancer (NSCLC). They cause immunerelated adverse events (irAEs), but the underlying mechanisms and predictors remain to be fully elucidated. In this retrospective study, we investigated the association between pretreatment neutrophil-to-lymphocyte ratio (NLR) and the occurrence of irAEs. Methods: The study involved 115 patients with NSCLC who started ICI-only treatment in our hospital between January 2016 and April 2020. Results: Forty-five patients (39.1%) had irAEs, and pretreatment NLR was significantly lower in the irAEs group than in the non-irAEs group (2.8 vs. 4.1; p = 0.036). The cutoff value of the NLR was 2.86 (area under curve, 0.62; sensitivity, 0.56; specificity, 0.71), and the incidence rate of irAEs was significantly higher in the NLR < 2.86 group than in the NLR ≥2.86 group (p = 0.004; odds ratio [OR]: 3.12; 95% confidence interval [CI]: 1.43-6.84). The multivariate analysis showed that the NLR was significantly associated with the occurrence of irAEs (p = 0.016; OR: 2.69; 95% CI: 1.21-6.01). Conclusions: Low pretreatment NLR may be a predictive factor for the occurrence of irAEs. By focusing on the potential risk of irAEs in patients with a low pretreatment NLR, irAEs can be appropriately managed from an early period.
K E Y W O R D Simmune checkpoint inhibitor, immune-related adverse event, neutrophil-to-lymphocyte rate, non-small cell lung cancer
What is known and objective
We investigated the elimination efficiency and pharmacokinetics (PK) parameters of vancomycin (VCM) in patients undergoing continuous haemodiafiltration (CHDF) using a polyethyleneimine‐coated polyacrylonitrile membrane (AN69ST) for dosage adjustment.
Methods
We conducted a retrospective study of CHDF patients treated with VCM from December 2017 to August 2019. We calculated PK parameters of VCM and determined the 24‐hour dose required to maintain the target trough concentration of VCM (VCM_trough).
Results and discussion
The average (95% CI) volume of distribution and total clearance of VCM were 75.5 L (63.7‐87.3 L) and 1.84 L/h (1.38‐2.30 L/h), respectively, and the elimination rate constant and half‐life were 0.026/h (0.017‐0.034/h) and 31.2 h (22.8‐39.5 h), respectively. The average AN69ST clearance of VCM (CL_CHDF) was 0.69 L/h (0.52‐0.86 L/h). The estimated average doses required to maintain VCM_trough of 10, 15 and 20 μg/mL were 623.1 mg (379.8‐866.4 mg), 934.6 mg (569.7‐1299.5 mg) and 1246.2 mg (759.6‐1732.8 mg), respectively.
What is new and conclusion
The PK of VCM and CL_CHDF of AN69ST were clarified. These results suggest that it is possible to adjust the dose of VCM in using AN69ST, which efficiently removes cytokines, and contributes to improvement of serious infections.
Background
Immunotherapy has become a standard‐of‐care for patients with non‐small‐cell lung cancer (NSCLC). Although several biomarkers, such as programmed cell death‐1, have been shown to be useful in selecting patients likely to benefit from immune checkpoint inhibitors (ICIs), more useful and reliable ones should be investigated. The prognostic nutritional index (PNI) is a marker of the immune and nutritional status of the host, and is derived from serum albumin level and peripheral lymphocyte count. Although several groups reported its prognostic role in patients with NSCLC receiving a single ICI, there exist no reports which have demonstrated its role in the first‐line ICI combined with or without chemotherapy.
Materials and Methods
Two‐hundred and eighteen patients with NSCLC were included in the current study and received pembrolizumab alone or chemoimmunotherapy as the first‐line therapy. Cutoff value of the pretreatment PNI was set as 42.17.
Results
Among 218 patients, 123 (56.4%) had a high PNI (≥42.17), while 95 (43.6%) had a low PNI (<42.17). A significant association was observed between the PNI and both the progression‐free survival (PFS; hazard ratio [HR] = 0.67, 95% confidence interval [CI]: 0.51–0.88, p = 0.0021) and overall survival (OS; HR = 0.46, 95% CI: 0.32–0.67, p < 0.0001) in the entire population, respectively. The multivariate analysis identified the pretreatment PNI as an independent prognosticator for the PFS (p = 0.0011) and OS (p < 0.0001), and in patients receiving either pembrolizumab alone or chemoimmunotherapy, the pretreatment PNI remained an independent prognostic factor for the OS (p = 0.0270 and 0.0006, respectively).
Conclusion
The PNI might help clinicians appropriately identifying patients with better treatment outcomes when receiving first‐line ICI therapy.
Purpose
Immune checkpoint inhibitors (ICI) ushered in a new era for the treatment of non-small cell lung cancer (NSCLC). However, they carry the risk of immune-related adverse events (irAEs). Recently, various studies have been conducted on the predictive factors for irAEs, but there are no reports focusing only on ICI plus platinum agents. The present study aimed to identify the risk factors for irAEs due to ICI combined with platinum-based chemotherapy in NSCLC patients, focusing only on the period of combined use.
Methods
This retrospective study included 315 NSCLC patients who started ICI combined with platinum-based chemotherapy treatment at 14 hospitals between December 2018 and March 2021. A logistic regression analysis was used to explore the predictive factors.
Results
A multivariate analysis revealed that squamous cell carcinoma (P = 0.021; odds ratio [OR]: 2.30; 95% confidence interval [Cl]: 1.14–4.65), anti-programmed death 1 antibody (anti-PD-1) plus anti-cytotoxic T-lymphocyte antigen-4 antibody (anti-CTLA-4) regimens (P < 0.01; OR: 22.10; 95% Cl: 5.60–87.20), and neutrophil-to-lymphocyte rate (NLR) < 3 (P < 0.01; OR: 2.91; 95% Cl: 1.35–6.27) were independent predictive factors for irAEs occurrence.
Conclusion
Squamous cell carcinoma, anti-PD-1 plus anti-CTLA-4 regimens, and NLR < 3 may be predictive factors for the occurrence of irAEs in patients with NSCLC due to ICI combined with platinum-based chemotherapy. By focusing on the potential risk of irAEs in patients with these factors, irAEs can be appropriately managed from an early stage.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.