Pan-immune-inflammation and its dynamics: predictors of survival and immune-related adverse events in patients with advanced NSCLC receiving immunotherapy

Abstract

Objectives: Pan-immune-inflammation value (PIV) is defined by the neutrophil, platelet, monocyte, and lymphocyte counts and is associated with immune-checkpoint inhibitor (ICI) therapy outcomes in advanced non-small cell lung cancer (aNSCLC). However, PIV is dynamic under therapy and its longitudinal assessment may help predict efficacy. This study investigated the impact of baseline PIV and its dynamics on ICI efficacy and its immune-related adverse events (irAEs). The study additionally attempted to understand the biological significance of PIV.

Patients and methods: This retrospective study analyzed the clinical data of 269 consecutive patients with aNSCLC. PIV was calculated at baseline and at weeks 3-4 to determine its association with overall survival (OS), progression-free survival (PFS), and irAEs.

Results: Results revealed that low baseline PIV was positively correlated with the incidence of irAEs. Moreover, a low PIV at baseline was significantly associated with a prolonged PFS (median PFS: 10 vs. 7 months, p = 0.0005) and OS (median OS: 29 vs. 21 months, p < 0.0001). When the PIV at baseline and weeks 3-4 was considered together, its low dynamics correlated with a higher incidence of irAEs (p = 0.001), a longer PFS (median PFS, 9 vs. 6 months, p = 0.012), and a longer OS (median OS; 28 vs. 21 months, p = 0.002).

Conclusion: Thus, PIV at baseline and its dynamics are novel and potent predictors of irAEs, PFS, and OS in patients with aNSCLC receiving immunotherapy. Moreover, the PIV dynamics may be an effective, novel surrogate marker to dynamically observe the efficacy of immunotherapy.

Keywords: Blood biomarkers; Dynamics; Immune-checkpoint inhibitors; Immune-related adverse events; Non-small-cell lung cancer; Pan-immune-inflammation value.

Fig. 1

Kaplan-Meier survival estimates according to baseline PIV and PIV dynamics. (A) Progression-free survival according to PIV at baseline. (B) Overall survival according to PIV at baseline. (C) Progression-free survival according to PIV dynamics. (D) Overall survival according to PIV dynamics

Fig. 2

PIV dynamic changes during the immunotherapy.(A) Comparison of PIV at baseline and week 3–4 from irAEs patients. (B) Comparison of PIV at baseline and week 3–4 from no irAEs patients. (C) Comparison of PIV dynamics between the irAEs and no irAEs patients. (D) PIV dynamics during baseline and week 3–4 in irAEs patients. (1 data point is outside the axis limits) (E) PIV dynamics during baseline and week 3–4 in no irAEs patients. (13 data points are outside the axis limits)