Positive Correlation of Peripheral CD8(+) T Lymphocytes with Immune-Related Adverse Events and Combinational Prognostic Value in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

SIMPLE SUMMARY: Immune checkpoint inhibitors are widely used in clinical practice and have demonstrated remarkable efficacy in advanced non-small cell lung cancer (NSCLC). However, their use is also commonly accompanied by immune-related adverse events (irAEs), and markers that are able to predict the onset of irAEs represent an urgent need. In this study, we found that the baseline level of peripheral CD8(+) T lymphocytes was the independent risk factor of the onset of irAEs, and it was associated with longer survival in advanced NSCLC patients treated with PD-1/PD-L1 inhibitors. Furthermore, the study showed the combinational predictive value of baseline CD8(+) T lymphocytes and the onset of irAEs for the clinical outcomes. ABSTRACT: Immune checkpoint inhibitors (ICIs) therapy has revolutionized the treatment patterns of non-small cell lung cancer (NSCLC). However, patients treated with ICIs may experience immune-related adverse events (irAEs). Markers that could predict the onset of irAEs are still unclear. Here, we report the possible correlation of baseline peripheral lymphocytes with irAEs and clinical outcomes in advanced NSCLC patients receiving ICIs. A total of 109 advanced NSCLC patients treated with ICIs from April 2017 to January 2021 were analyzed retrospectively. Logistic and Cox regression analyses was applied to evaluate independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). Among these patients, 55 (50.5%) patients experienced irAEs. The level of CD8(+) T lymphocytes at baseline was the independent risk factor for the onset of irAEs (p = 0.008). A higher level of CD8(+) T lymphocytes was associated with longer PFS (11.0 months vs. 3.0 months, p < 0.001) and OS (27.9 months vs. 11.7 months, p = 0.014). Furthermore, patients who had higher baseline CD8(+) T lymphocytes and experienced irAEs had a longer PFS (18.4 months vs. 2.2 months, p < 0.001) and OS (32.8 months vs. 9.0 months, p = 0.001) than those who had lower CD8+ T lymphocytes and no irAEs. Our study highlights the value of baseline peripheral CD8(+) T lymphocytes as a predictive factor for irAEs in advanced NSCLC patients receiving ICIs. In addition, patients who have higher baseline CD8(+) T lymphocytes and experience irAEs would have a superior PFS and OS.