Background Pembrolizumab is an anti-programmed cell death protein 1 (PD-1) antibody used for the treatment of advanced non-small cell lung carcinoma (NSCLC). Systemic inflammation has long been associated with poor outcomes in many types of solid tumors.1 Peripheral blood biomarkers such as absolute lymphocyte count (ALC) and absolute neutrophil count to absolute lymphocyte count ratio (ANC/ALC) serve as surrogate markers of inflammation. The aim of this study is to investigate ALC and ANC/ALC in patients with advanced NSCLC receiving pembrolizumab and determine if there is a correlation between these biomarkers and overall survival (OS).
Methods A total of 240 patients with advanced NSCLC treated with pembrolizumab at Northwell Health hospital centers were included. The ALC and ANC/ALC were examined at initiation of pembrolizumab and after 6 weeks on treatment. The prognostic role of these peripheral blood biomarkers on OS were examined with Kaplan-Meier curves and a multivariable cox regression analysis.
Results Of the 240 patients, the majority were male (52%), with a median age of 67 years (interquartile range [IQR] 59–73 years), had a diagnosis of adenocarcinoma (76%), with stage IV disease (82%). PDL-1 expression was >50% in 44% of the patients. The median time on treatment with pembrolizumab was 5.7 months [IQR: 2.7–12.5]. The median ALC and ANC/ALC were significantly lower at 6 weeks of pembrolizumab compared to the start date of treatment (1.38 vs. 1.4, p<0.001) and (3.6 vs. 4.6, p<0.001) respectively. An ALC greater than 1.4 was associated with an increased OS (figure 1), at 6 weeks after initiation of pembrolizumab (p=0.046), but not at the start of treatment (p=0.095). An ANC/ALC less than 5 was associated with improved OS (figure 2), both at initiation of pembrolizumab (p=0.003) and at 6 weeks after initiation of treatment (p = 0.028). Likewise, after adjusting for potential cofounders with a multivariate analysis (table 1), a baseline ANC/ALC of 5 or higher had a significantly increased risk of death (hazards ratio (HR)=1.84; 95% confidence interval (CI), 1.21–2.79; p=0.004), compared with patients with a lower ratio.
Conclusions High ALC at time of diagnosis as well as low ANC/ALC at baseline and at 6 weeks on treatment correlated with an increased OS in patients with advanced NSCLC treated with pembrolizumab. These findings represent a readily available predictive biomarker for oncologists and may help with risk stratification and strategizing treatment plans.
Ethics Approval The study was approved by Zucker School of Medicine at Hofstra/Northwell at Staten Island University Hospital’s IRB #: 19–0922
Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.
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