Table 2.
Factors associated with occurrence of all-grade and high-grade rechallenged irAEs.
| High-grade irAEs | All-grade irAEs | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n (total numbers, %) a | Univariate analysis | Multivariate analysis | n (total numbers, %) a | Univariate analysis | Multivariate analysis | |||||||
| Recurrence | Non-recurrence | OR (95% CI) | p | OR (95% CI) | p | Recurrence | Non-recurrence | OR (95% CI) | p | OR (95% CI) | p | |
| Age | 56.91 ± 10.13 | 63.11 ± 12.26 | 0.96 (0.91, 1.01) | 0.126 | / | / | 59.86 ± 12.47 | 62.69 ± 12.16 | 0.98 (0.94, 1.02) | 0.333 | / | / |
| Gender (male) | 8 (11, 72.7%) | 35 (55, 63.6%) | 0.66 (0.16, 2.76) | 0.565 | / | / | 19 (29, 65.5%) | 28 (45, 62.2%) | 0.87 (0.33, 2.30) | 0.774 | / | / |
| Types of initial irAEs | ||||||||||||
| Gastrointestinal b | 5 (11, 45.5%) | 6 (55, 10.9%) | 6.81 (1.58, 29.26) | 0.010 | 1.25 (0.16, 9.75) | 0.829 | 6 (29, 20.7%) | 6 (45, 13.3%) | 1.70 (0.49, 5.88) | 0.405 | / | / |
| Nephritic | 1 (11, 9.1%) | 2 (55, 3.6%) | 2.65 (0.22, 32.08) | 0.444 | / | / | 1 (29, 3.4%) | 2 (45, 4.4%) | 0.77 (0.07, 8.87) | 0.832 | / | / |
| Hematologic | 2 (11, 18.2%) | 7 (55, 12.7%) | 1.52 (0.27, 8.55) | 0.632 | / | / | 3 (29, 10.3%) | 7 (45, 15.6%) | 0.63 (0.15, 2.65) | 0.525 | / | / |
| Neurologic | 1 (11, 9.1%) | 8 (55, 14.5%) | 0.59 (0.07, 5.24) | 0.634 | / | / | 6 (29, 20.7%) | 4 (45, 8.9%) | 2.67 (0.68, 10.46) | 0.158 | / | / |
| Endocrine | 0 (11, 0.0%) | 7 (55, 12.7%) | NA | 0.999 | / | / | 1 (29, 3.4%) | 7 (45, 15.6%) | 0.19 (0.02, 1.67) | 0.135 | / | / |
| Respiratory | 2 (11, 18.2%) | 10 (55, 18.2%) | 1.00 (0.19, 5.36) | 1.000 | / | / | 7 (29, 24.1%) | 8 (45, 17.8%) | 1.47 (0.47, 4.62) | 0.508 | / | / |
| Ocular | 0 (11, 0.0%) | 2 (55, 3.6%) | NA | 0.999 | / | / | 2 (29, 6.9%) | 1 (45, 2.2%) | 3.26 (0.28, 37.69) | 0.344 | / | / |
| Rheumatologic | 0 (11, 0.0%) | 8 (55, 14.5%) | NA | 0.999 | / | / | 3 (29, 10.3%) | 5 (45, 11.1%) | 0.92 (0.20, 4.20) | 0.917 | / | / |
| Dermatologic | 0 (11, 0.0%) | 5 (55, 9.1%) | NA | 0.999 | / | / | 0 (29, 0.0%) | 5 (45, 11.1%) | NA | 0.999 | / | / |
| Initial irAE grade c | 2.96 (0.57, 15.49) | 0.198 | / | / | 0.71 (0.26, 1.96) | 0.504 | / | / | ||||
| Low-grade | 2 (10, 20.0%) | 20 (47, 42.6%) | 12 (25, 48.0%) | 15 (38, 39.5%) | ||||||||
| High-grade | 8 (10, 80.0%) | 27 (47, 57.4%) | 13 (25, 52.0%) | 23 (38, 60.5%) | ||||||||
| Initial corticosteroid dosage d | NA | 0.999 | / | / | 1.27 (0.28, 5.68) | 0.757 | / | / | ||||
| Low/moderate dose | 0 (8, 0.0%) | 9 (44, 20.5%) | 3 (22, 13.6%) | 6 (36, 16.7%) | ||||||||
| High dose | 8 (8, 100.0%) | 35 (44, 79.5%) | 19 (22, 86.4%) | 30 (36, 83.3%) | ||||||||
| Cancer type | ||||||||||||
| Melanoma | 6 (11, 54.5%) | 29 (55, 52.7%) | 1.08 (0.29, 3.95) | 0.912 | / | / | 18 (29, 62.1%) | 23 (45, 51.1%) | 1.57 (0.61, 4.05) | 0.356 | / | / |
| Lung | 3 (11, 27.3%) | 12 (55, 21.8%) | 1.34 (0.31, 5.86) | 0.694 | / | / | 5 (29, 17.2%) | 10 (45, 22.2%) | 0.73 (0.22, 2.40) | 0.604 | / | / |
| Renal | 1 (11, 9.1%) | 1 (55, 1.8%) | 5.40 (0.31, 93.61) | 0.247 | / | / | 2 (29, 6.9%) | 0 (45, 0.0%) | NA | 0.999 | / | / |
| Hematologic | 0 (11, 0.0%) | 6 (55, 10.9%) | NA | 0.999 | / | / | 2 (29, 6.9%) | 6 (45, 13.3%) | 0.48 (0.09, 2.57) | 0.392 | / | / |
| Initial ICI types | ||||||||||||
| PD-1/PD-L1 b | 4 (11, 36.4%) | 38 (55, 69.1%) | 0.26 (0.07, 0.99) | 0.049 | 0.46 (0.06, 3.37) | 0.448 | 14 (29, 48.3%) | 31 (45, 68.9%) | 0.42 (0.16, 1.11) | 0.079 | 0.57 (0.19, 1.71) | 0.312 |
| CTLA-4 | 3 (11, 27.3%) | 4 (55, 7.3%) | 4.78 (0.90, 25.46) | 0.067 | 1.16 (0.11, 12.40) | 0.904 | 5 (29, 17.2%) | 3 (45, 6.7%) | 2.92 (0.64, 13.29) | 0.167 | / | / |
| Combination | 4 (11, 36.4%) | 13 (55, 23.6%) | 1.85 (0.47, 7.32) | 0.383 | / | / | 10 (29, 34.5%) | 11 (45, 24.4%) | 1.63 (0.58, 4.53) | 0.352 | / | / |
| Time interval between initial irAEs and ICI rechallenge (weeks) b | 24.0 (11.5, 100.0) | 10.0 (4.0, 25.0) | 1.02 (1.00, 1.05) | 0.031 | 1.02 (1.00, 1.04) | 0.089 | 13.0 (5.0, 43.0) | 14.0 (5.0, 29.0) | 1.01 (0.99, 1.03) | 0.295 | / | / |
| Rechallenged ICI types | ||||||||||||
| PD-1/PD-L1 b | 7 (11, 63.6%) | 47 (55, 85.5%) | 0.30 (0.07, 1.26) | 0.099 | 0.43 (0.06, 2.91) | 0.387 | 20 (29, 69.0%) | 40 (45, 88.9%) | 0.28 (0.08, 0.94) | 0.039 | 0.56 (0.10, 3.25) | 0.517 |
| CTLA-4 | 2 (11, 18.2%) | 4 (55, 7.3%) | 2.83 (0.45, 17.83) | 0.267 | / | / | 5 (29, 17.2%) | 2 (45, 4.4%) | 4.48 (0.81, 24.87) | 0.086 | 2.24 (0.23, 21.42) | 0.485 |
| Combination | 2 (11, 18.2%) | 4 (55, 7.3%) | 2.83 (0.45, 17.83) | 0.267 | 4 (29, 13.8%) | 3 (45, 6.7%) | 2.24 (0.46, 10.84) | 0.316 | ||||
CI, confidence interval; CTLA-4, cytotoxic T-lymphocyte antigen-4; ICIs, immune checkpoint inhibitors; irAEs, immune-related adverse events; NA, not applicable; OR, odds ratio; PD-1, programmed cell death protein-1; PD-L1, programmed cell death protein ligand-1.
Qualitative variables were reported as n (total numbers, %), and quantitative variables were reported as mean ± standard deviation (SD) or a median with interquartile range (IQR).
Clinical factors of patients with p-values <0.05.
Initial irAE grade: low-grade was considered as grades 1–2, and high-grade was considered as grade ≥3.
Low-dose was considered as “prednisone ≤ 7.5 mg/day” or “methylprednisolone ≤ 6 mg/day”; moderate-dose was considered as “7.5 mg/day < prednisone ≤ 30 mg/day” or “6 mg/day < methylprednisolone ≤ 24 mg/day”; high-dose was considered as “prednisone > 30 mg/day” or “methylprednisolone > 24 mg/day.”
All significant p values are emphasized in bold.