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Table 3 : Clinical characteristics of patients with ICI induced neurotoxicities

From: Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study

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)
  1. aData available = 100% unless noted
  2. 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