Translational relevance of baseline peripheral blood biomarkers to assess the efficacy of anti-programmed cell death 1 use in solid malignancies

Abstract

Background: This study is an overall clinical analysis of anti-programmed cell death 1 (PD1) antibodies used in a single institution, emphasizing the role of baseline peripheral blood markers as a prognostic or predictor biomarker of immunotherapy.

Methods: Sixty-one patients were retrospectively analyzed from hospital medical records. The endpoint of this study was death from any cause and the survival time was calculated from the date of start of immunotherapy to the date of death. Descriptive and survival statistics was performed using SPSS version 23. Cutoff values for baseline biomarkers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], neutrophil-to-eosinophil ratio [NER], and lymphocyte-to-monocyte ratio [LMR]) were obtained using cutp function of Evaluate Cutpoints software (R survMisc package). Pearson and Pearman correlation coefficients were used to examine the relationship of peripheral blood biomarkers.

Results: Nighty-eight percent of the study population had Stage IV disease and total median overall survival postanti-PD1 therapy was 10.7 months. Patients receiving more than 5 doses of anti-PD1 therapy (12.6 m vs. 4.4 m, P < 0.001) and used in front lines (18.9 m vs. 10.7 m vs. 10.1 m vs. 2.8 m in first line, second line, third line, and >3 lines, respectively, P = 0.049) were found to have an impact in overall survival. Pembrolizumab showed a better survival compared to nivolumab (17.4 m vs. 8.2 m, P = 0.049) in our study. Among baseline biomarkers assessed, NLR (cutoff - 2.81, P = 0.003) and LMR (cutoff - 5.76, P = 0.017) has shown a statistically significant relationship with immunotherapy response. NER (cutoff - 24.32, P = 0.051) and PLR (cutoff - 190.8, P = 0.072) were also found to exhibit a strong relationship with anti-PD1 therapy response. NLR exhibits a statistically significant positive correlation with PLR (r = 0.917 P < 0.001) and NER (r = 0.400 P = 0.014).

Conclusion: Real-life data analysis of anti-PD1 use for solid cancers highlights that baseline NLR, PLR, NER, and LMR have a significant role as immunotherapy biomarkers. However, larger studies are required to further prove the specificity and sensitivity.

Keywords: Anti-programmed cell death 1 therapy; lymphocyte-to-monocyte ratio; neutrophil-to-eosinophil ratio; neutrophil-to-lymphocyte ratio; peripheral blood biomarkers; platelet-to-lymphocyte ratio.