3.1 Patient characteristics
All 95 patients received anti-PD-1/PD-L1 inhibitor treatment. The patient characteristics are summarized in Table 1. The median age was 62 years (range, 30–80 years); most patients (64.2%) exhibited an ECOG PS of 1. First-line and second-line treatments with anti-PD-1/PD-L1 therapy were recorded in 65% of patients. The median PFS was 108 days. There were zero cases of CR (0%), 12 cases of PR (12.6%), 49 cases of SD (51.6%), and 34 cases of PD (35.8%). The ORR and DCR were 12.6% and 64.2%, respectively.
The incidence of irAEs was 55.8%. Rash, immune-associated pneumonia, and hepatotoxicity were present in eight, seven, and 11 patients, respectively (Table 2).
3.2 Associations between irAEs and anti-PD-1/PD-L1 inhibitor responses
ORR in the irAEs and no-irAEs groups were 13.2% and 11.9%, respectively; corresponding DCRs were 60.4% and 69.0%. There were no significant differences in ORR and DCR between the two groups (P = 0.763 and P = 0.381; Table 3).
Considering the immortal time bias of irAEs, PFS was studied using landmark analysis (Fig. 1). Using 120 days as a threshold, the survival data were divided into two sections for survival analysis and a Kaplan–Meier curve was generated. The risk of disease progression was 0.981-fold in the irAEs group, compared with the risk in the no-irAEs group; there was no significant difference in PFS between the two groups (P = 0.951). After 120 days, the risk of disease progression was 0.398-fold in the irAEs group, compared with the risk in the no-irAEs group; the PFS was better in the irAEs group than in the no-irAEs group (P = 0.030).
3.3 Peripheral blood predictive markers for irAEs
Using irAEs as the result variable, we generated ROC curves of NLR, PLR, and AEC; the respective cutoff values selected were 8.58, 180.68, and 0.045 × 109/L. Based on cutoff value grouping, we compared the incidences of irAEs among groups; the incidences of irAEs were higher in the low NLR group (59.3%) than in the high NLR group (22.2%; P = 0.041; Table 3). In addition, the incidence of irAEs was significantly higher in the high-AEC group (63.0%) than in the low-AEC group (31.8%; P = 0.010; Table 4).
3.4 Univariate and multivariate logistic analysis of predictive markers for irAEs
The results of univariate and multivariate logistic analyses are shown in Table 5. In univariate logistic analysis, good ECOG score (0–1), low-NLR (cutoff value: 8.58), and high-AEC (cutoff value: 0.045 × 109/L) were important predictors of irAEs (P = 0.0499, OR: 0.196, 95% CI: 0.038–1.000; P = 0.0499, OR: 0.507, 95% CI: 0.241–1.065; P = 0.012, OR: 3.651, 95% CI: 1.322–10.076). Multivariate logistic analysis was performed involving factors with P < 0.2 in univariate analysis and tumor species; high-AEC and good ECOG score were independently associated with irAEs (P = 0.014, OR: 4.114, 95% CI: 1.328–12.858; P = 0.046, OR: 0.159, 95% CI: 0.026–0.970). In addition, immunotherapy combined with targeted therapy was associated with a greater risk of irAEs, compared with other treatments (P = 0.005, OR: 0.156, 95% CI: 0.045–0.544).
3.5 Forest plot of multivariate logistic regression analyses for irAEs
To more intuitively depict the results of multivariate logistic analysis of irAEs, we generated a forest plot with irAEs as the study event (Fig. 2). .The incidence of irAEs was higher in the high-AEC group than in the low-AEC group; the incidence of irAEs was greater in the good ECOG PS (0–1) group than in the ECOG PS (2) group. Similarly, the incidence of irAEs was lower in patients receiving immunotherapy combined with targeted therapy, compared with patients receiving other treatments.
3.6 Associations of baseline AEC with anti-PD-1/PD-L1 efficacy
The ORRs of the high-AEC (> 0.045 × 109/L) and low-AEC (≤ 0.045 × 109/L) groups were 9.5% and 22.7%, respectively; the corresponding DCRs were 64.3% and 63.6%. There were no significant differences in ORR (P = 0.208) or DCR (P = 0.949) between the two groups (Table 6). The median PFSs in the high-AEC (> 0.045 × 109/L) and low-AEC (≤ 0.045 × 109/L) groups were 168 and 116 days, respectively (P = 0.0295; Fig. 3).