Results

Baseline characteristics

This study included 167 patients who received anti-PD1 treatment with pembrolizumab after failure of first-line chemotherapy. The clinical characteristics of the patients and relations with response on the first CT scan are summarized in Table 1. The mean age was 60.2 ±6.8 years; most of the patients were men (64%), and almost all patients exhibited an ECOG PS of 1 (98%). The lung was the most common metastatic site (73%), followed by pleural effusion (59%) and bone (40%). All patients were eligible for the examination of tumor PD-L1 expression, of which 13 patients (7.8%) had expression in more than 50%, 80 patients (47.9%) had expression in 25-49%, and 74 patients (44.3%) had expression in 1-24%. Of all the clinicopathological characteristics of the patients, only NLR2, PLR2 and the presence of sarcopenia were significantly related to the response on the first CT scan (Table 1).

Hematological biomarkers and their relation to response on the first CT scan

On the first CT scan after chemotherapy treatment, 15 (8.9%) patients showed progressive disease. After treatment with pembrolizumab on the first CT scan evaluation, these 15 patients were subdivided as follows: 8 hyperprogressors (HPs), 1 pseudoprogressor (PP) and 6 nonprogressors (NPs). These 15 patients had significantly higher NLR1 and PLR1 than the patients without progressive disease (7.49±2.8 vs 4.31±2.45; 283.3±96.5 vs 207±102.6, respectively). Twelve of them had an NLR>5, and at least 9 (∆PMMA was not available for 3) of them had ∆PMMA≥10%.
On the first CT scan after immunotherapy treatment, 45 (26.9%) patients showed progressive disease, and at least 25 (∆PMMA was not available for 7) of them had ∆PMMA≥10%. Of them, 16 patients (9.6%) were classified as HPs, 5 (2.9%) were classified as PPs, and the remaining 24 (14%) were classified as Ps. Patients with pseudoprogression were without any clinical deterioration and received further treatment with immunotherapy for another 8 weeks, when the control CT scan proved a partial response for 3 patients and stable disease for 2 patients; the response lasted for at least 6 months. Of all HPs, 15 (93%) had an NLR>5. HPs had higher mean values of NLR2, PLR2 and ∆NLR, but not higher ∆PLR values, than Ps or NPs (Table 2). There was no significant difference in hematological parameters between HPs and PPs, Ps and NPs, Ps and PPs, or NPs and PPs, except for NLR2, for which NPs had significantly lower values than PPs (Table 2).
ROC analysis was performed to explore the potential predictive role of these biomarkers, NLR2, PLR2, ΔNLR, and ΔPLR, as noninvasive biomarkers for discrimination between patients with or without HPD (Table 3). At the optimal cutoff values for NLR2, the biomarker could significantly and well distinguish between patients with or without HPD (AUC = 0.85, 95% CI: 0.75- 0.95, p < 0.001) with a sensitivity of 87.5% and a specificity of 68.9%. PLR2 also allowed significant but fair discrimination between patients with and without HPD (AUC = 0.79, 95% CI: 0.66- 0.92, p < 0.001) with a sensitivity of 75.0% and a specificity of 64.1% (Figure 1A and B). ΔNLR could also discriminate between patients with and without HPD, but poorly (Table 3). The Wilcoxon test showed that the ALC and APC did not change significantly from chemotherapy. Nevertheless, the ANC significantly differed between the first cycle of chemotherapy and the first pembrolizumab infusion. The McNemar test showed that the proportion of patients with an NLR>5 and a high PLR did not change significantly with chemotherapy treatment.
A significantly strong correlation was detected between NLR1 and PLR1 (rho=0.763) and NLR2 and PLR2 (rho=0.785), and a moderate correlation was detected between ΔNLR and ΔPLR (rho=0.465).