1929O - Soluble PD-L1 and circulating CD8+PD1+ and NK cells enclose a highly prognostic and predictive immune effector score in immunotherapy treated NSCLC patients

Background

Upfront criteria to foresee immune checkpoint inhibitors (ICI) efficacy are far from being identified. Thus, we integrated blood descriptors of pro-inflammatory/immunosuppressive or effective anti-tumor response to define predictive immune profiles in ICI-treated advanced NSCLC.

Methods

Peripheral blood (PB) was prospectively collected at baseline from 109 consecutive NSCLC patients undergoing ICI as first or more line treatment. Soluble PD-L1 (sPD-L1) (immunoassay), CD8+PD1+ and NK cells (FACS) were assessed and integrated to generate an Immune effector Score (I_effS). Lung Immune Prognostic Index (LIPI) was also computed by LDH levels and derived Neutrophil-to-Lymphocyte Ratio (dNLR). All these parameters were correlated with survival outcome and response to treatment.

Results

High sPD-L1 and low PB number of CD8+PD1+ and NK cells, individually had a negative impact on both PFS (P<0.001) and OS (P<0.01) as well as on ICI-response (P<0.05). Thus, sPD-L1^high, CD8+PD1+^low and NK^low were considered as risk factors encompassing I_effS, whose prognostic power outperformed that of single features and slightly exceeded that of LIPI. Accordingly, the absence of these pre-determined risk factors portrayed a favorable I_effS able to identify NSCLC patients with significantly prolonged PFS (median NR vs 2.3 months, P<0.001) and OS (median NR vs 4.1, P<0.001) and greater benefit from ICI (P<0.01). We then combined each individual risk parameter composing I_effS and LIPI (LDH^high, dNLR^high), thus defining three distinct prognostic classes: 0-1 vs 2-3 vs ≥ 4 risk factors. A remarkable impact of I_effS-LIPI integration was documented in terms of survival outcome (PFS: HR, 4.61; 95% CI, 2.32-9.18; P<0.001; OS: HR, 4.03; 95% CI, 1.91-8.67; P<0.001) and response to ICI (ROC curve AUC=0.90, 95% CI 0.81-0.97, P<0.001).

Conclusions

Composite risk models based on blood parameters featuring the tumor-host interaction might provide non-invasive prognostic and predictive scores in ICI-treated advanced NSCLC patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

University Hospital of Parma.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.