Table 3.
: Clinical characteristics of patients with ICI induced neurotoxicities
| Characteristics | Myasthenia gravis N (%)a |
Encephalitis/ myelitis N (%)a |
Guillain-Barre syndrome N (%)a |
Non-infectious meningitis N (%)a |
|---|---|---|---|---|
| Total number | 228 | 250 | 122 | 72 |
| Reporting year | ||||
| 2018 (through September) | 101 (44.30) | 107 (42.80) | 45 (36.9) | 20 (27.78) |
| 2017 | 73 (32.02) | 90 (36.00) | 46 (37.7) | 24 (33.33) |
| 2016 | 39 (17.11) | 38 (15.20) | 17 (13.9) | 13 (18.06) |
| 2015 | 12 (5.26) | 8 (3.20) | 7 (5.7) | 9 (12.50) |
| 2014 | 3 (1.32) | 3 (1.20) | 6 (4.9) | 3 (4.17) |
| 2012–2013 | 0 | 4 (1.60) | 1 (0.82) | 3 (4.17) |
| Gender | ||||
| Male | 125 (60.98) | 140 (63.35) | 71 (65.74) | 35 (53.03) |
| Female | 80 (39.02) | 81 (36.94) | 37 (34.26) | 31 (46.97) |
| Data available | 205 (89.91) | 221 (88.40) | 108 (88.52) | 66 (91.67) |
| Age at onset, mean ± SD, years | 70.28 ± 10.50 | 58.69 ± 15.98 | 65.01 ± 14.41 | 56.25 ± 14.63 |
| [min-max] | [32–86] | [7–86] | (25–98) | [28, 86] |
| Data available | 122 (53.51) | 162 (64.80) | 76 (62.29) | 51 (70.83) |
| Drugs | ||||
| Monotherapy with Anti PD-1/PD-L1 | 197 (86.40) | 186 (74.40) | 64 (52.46) | 36 (50.00) |
| - Nivolumab | 68 (34.52) | 127 (68.28) | 33 (51.56) | 23 (63.89) |
| - Pembrolizumab | 116 (58.88) | 36 (19.35) | 27 (42.19) | 9 (25.00) |
| - Atezolizumab | 9 (4.57) | 20 (10.58) | 3 (4.69) | 4 (11.11) |
| - Durvalumab | 1 (0.51) | 3 (1.59) | 0 (0) | 0 (0) |
| - Avelumab | 3 (1.52) | 0 (0) | 1 (0.82) | 0 (0) |
| Monotherapy with Anti CTLA-4 | 14 (6.14) | 21 (8.40) | 37 (30.33) | 20 (27.78) |
| - Ipilimumab | 14 (100) | 20 (100) | 37 (100) | 20 (100) |
| Combination therapy | 17 (7.46) | 43 (17.20) | 21 (17.21) | 16 (22.22) |
| - Nivolumab + Ipilimumab | 15 (88.24) | 40 (93.02) | 20 (95.24) | 16 (100) |
| - Pembrolizumab + Ipilimumab | 1 (5.88) | 3 (6.98) | 1 (4.76) | 0 (0) |
| - Tremelimumab + Durvalumab | 1 (5.88) | 0 (0) | 0 (0) | 0 (0) |
| Indications | ||||
| Lung cancer | 73 (39.67) | 90 (38.96) | 18 (18.75) | 7 (11.11) |
| Malignant melanoma | 47 (25.54) | 56 (24.24) | 65 (67.71) | 38 (60.32) |
| Renal cell carcinoma | 25 (13.59) | 13 (5.62) | 5 (5.21) | 5 (7.94) |
| Other | 39 (21.20) | 51 (20.40) | 8 (8.33) | 13 (20.63) |
| Data available | 184 (80.70) | 231 (85.20) | 96 (78.69) | 63 (87.50) |
| Time to irAE onset, days: | ||||
| Median, [IQR] | 29 [24–53] | 61 [18–153] | 65.5 [29–124] | 68 [27–134] |
| [min-max] | [6–132] | [1–841] | [2–995] | [8–400] |
| Data available | 45 (19.74) | 72 (28.80) | 34 (27.87) | 23 (31.51) |
| Death | 44 (19.30) | 32 (12.80) | 13 (10.66) | 6 (8.33) |
| Concurrent neurologic symptoms/syndromes | ||||
| Myasthenia gravis | N/A | 1 (0.40) | 1 (0.82) | 0 (0) |
| Encephalitis/myelitis | 1 (0.44) | N/A | 1 (0.82) | 5 (6.94) |
| Cerebral vasculitis | 0 (0) | 1 (0.40) | 0 (0) | 1 (1.39) |
| Guillain Barre syndrome | 1 (0.44) | 1 (0.40) | N/A | 2 (2.78) |
| Peripheral Neuropathy | 0 (0) | 4 (1.60) | N/A | 0 (0) |
| Meningitis | 0 (0) | 5 (5.00) | 2 (1.64) | N/A |
| Demyelination | 0 (0) | 5 (2.00) | 0 (0) | 0 (0) |
| Seizure | 1 (0.44) | 10 (4.00) | 0 (0) | 0 (0) |
| Stroke | 0 (0) | 2 (0.80) | 0 (0) | 4 (5.56) |
| Blindness (unilateral or bilateral) | 1 (0.44) | 0 (0) | 0 (0) | 0 (0) |
| Coma/loss of consciousness | 1 (0.44) | 4 (1.60) | 0 (0) | 0 (0) |
| Other irAEs | ||||
| Colitis/diarrhea | 4 (1.75) | 4 (1.60) | 3 (2.46) | 3 (4.17) |
| Pneumonitis | 1 (0.44) | 5 (2.00) | 0 (0) | 2 (2.78) |
| Myocarditis | 20 (10.52) | 3 (1.20) | 0 (0) | 1 (1.39) |
| Myositis | 37 (16.23) | 2 (0.80) | 0 (0) | 1 (1.39) |
| Dermatitis | 2 (0.88) | 12 (4.80) | 3 (2.46) | 3 (4.17) |
| Thyroiditis/hypothyroidism | 7 (3.07) | 6 (2.40) | 5 (4.10) | 1 (1.39) |
| Hypophysitis/hypopituitarism | 0 (0) | 5 (2.00) | 1 (0.82) | 5 (6.94) |
| Hepatitis | 11 (4.82) | 2 (0.80) | 3 (2.46) | 1 (1.39) |
| Nephritis | 0 (0) | 2 (0.80) | 0 (0) | 1 (1.39) |
| Other | 3 (1.32) | 10 (4.00) | 2 (1.64) | 7 (9.72) |
| None | 154 (67.54) | 205 (82.00) | 110 (90.16) | 46 (63.89) |
aData available = 100% unless noted
Abbreviations: CTLA-4 cytotoxic T-lymphocyte-associated protein 4, ICI immune checkpoint inhibitor, IQR interquartile range, irAE immune related adverse event, [min-max] minimum-maximum, PD-1 programmed cell death protein 1, PD-L1 programmed cell death ligand 1, SD standard deviation, N/A not applicable