Peripheral blood markers predictive of outcome and immune-related adverse events in advanced non-small cell lung cancer treated with PD-1 inhibitors

Abstract

Background Selected patients with advanced non-small cell lung cancer (NSCLC) benefit from immunotherapy, especially immune checkpoint inhibitors such as PD-1 (programmed cell death protein 1) inhibitor. Peripheral blood biomarkers would be most convenient to predict treatment outcome and immune-related adverse events (irAEs) in candidate patients. This study explored associations between inflammation-related peripheral blood markers and onset of irAEs and outcome in patients with advanced NSCLC receiving PD-1 inhibitors. Methods A retrospective analysis was conducted of 102 patients with advanced NSCLC receiving PD-1 inhibitors from January 2017 to May 2019. Cox regression models were employed to assess the prognostic effect of low/high neutrophil/ lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and prognostic nutrition index (PNI) on overall survival (OS) and progression-free survival (PFS). Logistic regression models were used to analyze the correlation between peripheral blood markers and the onset of irAEs. Result NLR < 5, LDH < 240 U/L, or PNI ≥ 45 was favorably associated with significantly better outcomes compared with higher, higher, or lower values, respectively. The multivariate analysis determined that these parameters were independently associated with both better PFS (p = 0.049, 0.046, 0.014, respectively) and longer OS (p = 0.007, 0.031, < 0.001, respectively). Patients with three favorable factors among NLR, LDH, and PNI had better PFS and OS than did those with two, one, or none. PNI and NLR were associated with the onset of irAEs. Conclusion In patients with advanced NSCLC treated with PD-1 inhibitors, pretreatment NLR, LDH, and PNI may be useful predictive markers of clinical outcome and irAEs.

Biomarkers of Checkpoint Inhibitor Induced Immune-Related Adverse Events—A Comprehensive Review

“…The development of irAEs has been associated with improved response to ICI treatment, as reviewed by Das & Johnson ( 80 ). In line with this, some of the irAE biomarkers in this review have also shown associations with ICI responses ( 18 – 22 , 31 , 37 , 44 ). This is not surprising, in view of the common underlying mechanism of irAEs and anti-tumor responses ( 48 ).…”

“…In their study amongst 102 anti-PD-1 treated melanoma patients, Peng et al. reported that patients with NLR>5 experienced less irAEs ( 18 ). Additionally, they observed that a prognostic nutrition index (PNI), which is calculated from the serum albumin level and total lymphocyte count, of 45 or higher was correlated with increased risk of irAEs.…”

Association of Blood Biomarkers and Autoimmunity with Immune Related Adverse Events in Patients with Cancer treated with Immune Checkpoint Inhibitors

“…Multiple prior studies have also shown the association between NLR, irAE development and OS (12)(13)(14). In a study of patients with advanced non-small cell lung cancer (NSCLC) treated with anti-PD-(L)1 agents, baseline NLR<3 was signi cantly associated with development of irAEs.…”

Peripheral Blood Markers Associated with Immune-Related Adverse Effects in Patients Who Had Advanced Non-Small Cell Lung Cancer Treated with PD-1 Inhibitors

“…This finding agrees with previous studies, which associated lower inflammation-related blood markers with a higher risk of irAEs in NSCLC patients. 24 , 25 While patients who had irAEs were more likely to have good treatment outcomes with anti-PD-1, they were also more likely to have lower baseline NLR and PLR levels. This result was consistent with the previous observation, that lower NLR and PLR were associated with good clinical outcomes in NSCLC patients treated with immune checkpoint inhibitors or platinum-based first-line chemotherapy.…”