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.

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Abstract 83 Figure 1

Kaplan-Meier survival estimates between groups with different ALC at the start date of pembrolizumab and at 6 weeks after initiation of pembrolizumab. There is a statistically significant difference in OS between patients with ALC < 1.4 and patients with ALC ≥ 1.4 at 6 weeks after initiation of pembrolizumab (p = 0.046), but not at the start of treatment (p = 0.095).

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Abstract 83 Figure 2

Kaplan-Meier survival estimates between groups with different ANC/ALC ratio at the start date of pembrolizumab and at 6 weeks after initiation of pembrolizumab. There is a statistically significant difference in OS between patients with ANC/ALC < 5 and patients with ALC ≥ 5, both at the start date of pembrolizumab (p = 0.003) and at 6 weeks after initiation of pembrolizumab (p = 0.028).

Ethics Approval The study was approved by Zucker School of Medicine at Hofstra/Northwell at Staten Island University Hospital’s IRB #: 19–0922

Reference

1. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.