Table 3. Univariate and stepwise multivariate analysis of risk factors for any grade of irAEs.
| Variables | Univariate analysis | Multivariate analysis | |||
|---|---|---|---|---|---|
| OR (95% CI) | P | OR (95% CI) | P | ||
| Age | |||||
| ≤60 years | 1 (reference) | 1 (reference) | |||
| >60 years | 0.61 (0.3–1.26) | 0.18 | 0.79 (0.35–1.77) | 0.56 | |
| Gender | |||||
| Male | 1 (reference) | 1 (reference) | |||
| Female | 0.98 (0.46–2.05) | 0.95 | |||
| ECOG performance status | 1.63 (0.49–5.44) | 0.42 | |||
| 0–1 | 1 (reference) | 1 (reference) | |||
| ≥2 | 0.25 (0.03–2.03) | 0.19 | 0.17 (0.02–1.67) | 0.13 | |
| Smoking history | |||||
| No | 1 (reference) | 1 (reference) | |||
| Yes | 1.02 (0.49–2.09) | 0.97 | 0.96 (0.3–3.02) | 0.94 | |
| Pathology | |||||
| Adenocarcinoma | 1 (reference) | 1 (reference) | |||
| Squamous cell carcinoma | 1.15 (0.56–2.37) | 0.71 | 0.87 (0.33–2.3) | 0.77 | |
| Adenosquamous carcinoma | 2.83 (0.37–21.55) | 0.31 | 0.81 (0.06–10.17) | 0.87 | |
| Large cell carcinoma | 0.72 (0.07-7.99) | 0.79 | 3.96 (0.35–44.21) | 0.26 | |
| Stage | |||||
| III | 1 (reference) | 1 (reference) | |||
| IV | 0.72 (0.32–1.61) | 0.43 | 0.72 (0.27–1.89) | 0.50 | |
| Driver gene mutations | |||||
| Negative | 1 (reference) | 1 (reference) | |||
| Positive | 0.80 (0.38–1.67) | 0.55 | 0.74 (0.23–2.46) | 0.63 | |
| Treatment lines | |||||
| First line | 1 (reference) | 1 (reference) | |||
| Second line | 0.78 (0.36–1.71) | 0.54 | 1.29 (0.38–4.4) | 0.68 | |
| Third line | 0.37 (0.1–1.38) | 0.14 | 0.41 (0.08–2.13) | 0.29 | |
| ≥ Fourth line | 0.53 (0.14–2.09) | 0.37 | 1 (0.15–6.52) | 1.00 | |
| Treatment received | |||||
| ICI monotherapy [anti-PD-(L)-1] | 1 (reference) | 1 (reference) | |||
| Combined immunotherapy [anti-PD-(L)1 & anti-CTLA4] | 1.93 (0.14–25.95) | 0.62 | 1.45 (0.06–32.97) | 0.82 | |
| Chemoimmunotherapy* | 1.50 (0.71–3.16) | 0.29 | 1.51 (0.48–4.79) | 0.49 | |
| ANA titers | |||||
| <1:320 | 1 (reference) | 1 (reference) | |||
| ≥1:320 | 2.42 (0.99–5.89) | 0.05 | 4.9 (1.45–16.52) | 0.01 | |
| ANA karyotypes | |||||
| None | 1 (reference) | 1 (reference) | |||
| S | 1.20 (0.53–2.72) | 0.67 | 0.78 (0.28–2.17) | 0.64 | |
| C | 1.64 (0.52–5.14) | 0.39 | 0.9 (0.25–3.31) | 0.88 | |
| H | 0.50 (0.10–2.45) | 0.39 | 0.22 (0.03–1.39) | 0.11 | |
| SN | 0 (0–0) | 1.00 | 0 | 1.00 | |
| HS | 2.74 (0.36–20.82) | 0.33 | 1 (0.09–11.17) | 1.00 | |
| N | 8.21 (0.8–83.83) | 0.08 | 7 (0.6–81.77) | 0.12 | |
*, chemoimmunotherapy means immunotherapy [anti-PD-(L)1 ± anti-CTLA4] combined with chemotherapy (platinum doublet or single drug chemotherapy including paclitaxel, docetaxel, pemetrexed and gemcitabine). irAEs, immune-related adverse events; ECOG, Eastern Cooperative Oncology Group; ICI, immune checkpoint inhibitor; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1; ANA, antinuclear antibody; S, speckled type; C, cytoplasmic type; H, homogeneous type; SN, speckled-nucleolar type; HS, homogeneous-speckled type; N, nucleolar type; OR, odds ratio; CI, confidence interval.