Table 5.
Top 10 ICI-related neurological complications belonging to the three most described High-Level Group Terms (HLGTs) in EudraVigilance until February 7, 2020, categorized by ICI treatments involved.
| Level | All ICIs | Anti-CTLA-4 | Anti-PD-1 | Anti-PD-L1 | Combination therapies | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| N = 6,429 | Ipilimumab | Nivolumab | Pembrolizumab | Cemiplimab | Durvalumab | Avelumab | Atezolizumab | Ipi/nivo | Others* | ||
| (100%) | N (%) | N (%) | N (%) | N (%) | N (%) | N (%) | N (%) | N (%) | N (%) | ||
| HLGT | “Neurological disorders NEC” | 2,066 (32.1) | 144 (7) | 850 (41.1) | 683 (33.1) | 6 (0.3) | 76 (3.7) | 21 (1) | 114 (5.5) | 163 (7.9) | 9 (0.4) |
| 1. Dizziness | 250 (12.1) | 23 (9.2) | 102 (40.8) | 80 (32) | – | 8 (3.2) | 5 (2) | 13 (5.2) | 17 (6.8) | 2 (0.8) | |
| 2. Hypoesthesia | 140 (6.8) | 13 (9.3) | 48 (34.3) | 49 (35) | – | 4 (2.9) | 1 (0.7) | 10 (7.1) | 15 (10.7) | – | |
| 3. Somnolence | 130 (6.2) | 5 (3.8) | 49 (37.7) | 46 (35.4) | – | 5 (3.8) | 3 (2.3) | 9 (7) | 13 (10) | – | |
| 4. Loss of consciousness | 108 (5.2) | 6 (5.6) | 39 (36.1) | 37 (34.2) | 1 (1) | 1 (1) | 1 (0.9) | 10 (9.2) | 13 (12) | – | |
| 5. Paraesthesia | 105 (5.1) | 8 (7.6) | 49 (46.7) | 28 (26.7) | – | 4 (3.8) | – | 7 (6.7) | 9 (8.5) | – | |
| 6. Altered state of consciousness | 92 (4.5) | 3 (3.3) | 36 (39.1) | 34 (37) | – | 1 (1.1) | 2 (2.2) | 7 (7.6) | 6 (6.5) | 3 (3.2) | |
| 7. Metastases to CNS | 86 (4.2) | 5 (5.8) | 47 (54.6) | 10 (11.6) | – | 13 (15.1) | – | 1 (1.2) | 9 (10.5) | 1 (1.2) | |
| 8. Syncope | 81 (4) | 9 (11.1) | 29 (35.8) | 25 (30.9) | 1 (1.2) | 3 (3.7) | 2 (2.5) | 5 (6.2) | 7 (8.6) | – | |
| 9. Dysgeusia | 72 (3.5) | 2 (2.8) | 32 (44.4) | 31 (43) | – | 1 (1.4) | – | 4 (5.6) | 2 (2.8) | – | |
| 10. Depressed level of consciousness | 72 (3.5) | 1 (1.4) | 31 (43) | 25 (34.7) | – | 4 (5.6) | 1 (1.4) | 7 (9.7) | 3 (4.2) | – | |
| HLGT | “Peripheral neuropathies” | 773 (12) | 115 (14.9) | 276 (35.7) | 204 (26.4) | 1 (0.1) | 17 (2.2) | 3 (0.4) | 52 (6.7) | 95 (12.3) | 10 (1.3) |
| 1. Neuropathy peripheral | 335 (43.3) | 49 (14.6) | 120 (35.8) | 90 (26.8) | 8 (2.4) | 33 (9.8) | 2 (0.6) | 30 (9) | 3 (1) | ||
| 2. Guillain–Barré syndrome | 154 (20) | 29 (18.8) | 46 (30) | 41 (26.6) | 2 (1.3) | 7 (4.5) | 25 (16.2) | 4 (2.6) | |||
| 3. Polyneuropathy | 69 (9) | 10 (14.5) | 24 (34.8) | 16 (23.2) | 1 (1.4) | 2 (2.9) | 4 (5.8) | 11 (16) | 1 (1.4) | ||
| 4. Peripheral sensory neuropathy | 42 (5.4) | 5 (11.9) | 17 (40.5) | 15 (35.7) | 3 (7.1) | 1 (2.4) | 1 (2.4) | ||||
| 5. Demyelinating polyneuropathy | 29 (3.8) | 6 (20.7) | 11 (38) | 5 (17.2) | – | – | 2 (6.9) | – | 5 (17.2) | ||
| 6. Neuritis | 19 (2.5) | 1 (5.3) | 9 (47.4) | 4 (21) | – | – | 1 (5.3) | – | 4 (21) | ||
| 7. Autoimmune neuropathy | 18 (2.3) | 2 (11.1) | 6 (33.3) | 4 (22.2) | – | 1 (5.6) | – | – | 5 (27.8) | ||
| 8. Carpal tunnel syndrome | 13 (1.7) | 1 (7.7) | 7 (53.8) | 5 (38.5) | – | – | – | – | |||
| 9. Chronic inflammatory demyelinating polyradiculoneuropathy | 12 (1.5) | 2 (16.7) | 4 (33.3) | 3 (25) | – | – | – | – | 2 (16.7) | 1 (8.3) | |
| 10. Peripheral motor neuropathy | 11 (1.4) | 1 (9.1) | 5 (45.4) | 4 (36.4) | – | – | – | – | 1 (9.1) | ||
| HLGT | “Central nervous system vascular disorders” | 624 (9.7) | 58 (9.3) | 244 (39.1) | 224 (36) | 1 (0.2) | 25 (4) | 2 (0.3) | 27 (4.3) | 39 (6.2) | 4 (0.6) |
| 1. Cerebrovascular accident | 146 (23.4) | 16 (11) | 48 (32.9) | 56 (38.3) | – | 8 (5.5) | – | 10 (6.8) | 7 (4.8) | 1 (0.7) | |
| 2. Cerebral infarction | 128 (20.5) | – | 48 (37.5) | 69 (54) | – | 4 (3.1) | – | 2 (1.5) | 5 (3.9) | – | |
| 3. Cerebral hemorrhage | 126 (29.2) | 21 (16.7) | 49 (38.9) | 29 (23) | – | 3 (2.4) | – | 5 (4) | 19 (15) | – | |
| 4. Ischemic stroke | 36 (5.8) | 2 (5.5) | 19 (52.8) | 12 (33.3) | – | 1 (2.8) | – | 1 (2.8) | 1 (2.8) | – | |
| 5. Hemorrhage intracranial | 25 (4) | 6 (24) | 10 (40) | 6 (24) | – | – | 1 (4) | 1 (4) | 1 (4) | – | |
| 6. Transient ischemic attack | 23 (3.7) | 1 (4.3) | 12 (52.3) | 4 (17.5) | 1 (4.3) | 1 (4.3) | – | 1 (4.3) | 1 (4.3) | 2 (8.7) | |
| 7. Cerebral ischemia | 17 (2.7) | 2 (11.8) | 6 (35.3) | 5 (29.4) | – | 3 (17.6) | – | – | 1 (5.9) | – | |
| 8. Lacunar infarction | 10 (1.6) | 1 (10) | 4 (40) | 5 (50) | – | – | – | – | – | – | |
| 9. Subarachnoid hemorrhage | 9 (1.4) | 1 (11.1) | 7 (77.8) | 1 (11.1) | – | – | – | – | – | – | |
| 10. Vasculitis cerebral | 9 (1.4) | – | 5 (55.6) | 3 (33.3) | – | – | 1 (11.1) | – | – | – | |
NEC, not elsewhere classified; HLGTs, High-Level Group Terms.
*stand for pembrolizumab/nivolumab/ipilimumab, pembrolizumab/atezolizumab, ipilimumab/pembrolizumab.