sas sytstem. the results include data from the following ... · ast increased keynote-006...
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SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Supplementary Table 1: Incidence per 1000 person-months of all grade and grade 3 to 5 adverse events under immunotherapy using the
SAS Sytstem. The results include data from the following studies: CA-184-002, KEYNOTE-001, KEYNOTE-001 (randomized cohorts),
KEYNOTE-002, KEYNOTE-006, CheckMate-037, CheckMate-066, CheckMate-067, and CheckMate-069.
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
ALT increased CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 55 26 14 [11;18] 7 [4;9]
ALT increased CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 21 10 20 [12;29] 10 [4;16]
ALT increased _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 76 36 16 [12;19] 7 [5;10]
ALT increased CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 2 0 1 [0;1] 0 [0;0]
ALT increased CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 12 5 3 [1;5] 1 [0;2]
ALT increased CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 2 0 4 [0;9] 0 [0;0]
ALT increased KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 9 2 4 [2;7] 1 [0;2]
ALT increased _ALL Ipilimumab 3 mg/kg Q3W 744 9964 25 7 3 [2;3] 1 [0;1]
ALT increased CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 7 2 3 [1;5] 1 [0;2]
ALT increased CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 3 2 1 [0;2] 1 [0;1]
ALT increased CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 12 4 3 [1;5] 1 [0;2]
ALT increased _ALL Nivolumab 3mg/kg Q2W 787 9604 22 8 2 [1;3] 1 [0;1]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
ALT increased KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 6 0 10 [2;17] 0 [0;0]
ALT increased KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 12 0 5 [2;9] 0 [0;0]
ALT increased _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 18 0 6 [3;9] 0 [0;0]
ALT increased KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 5 0 8 [1;15] 0 [0;0]
ALT increased KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
ALT increased _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 7 0 5 [1;9] 0 [0;0]
ALT increased KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
ALT increased KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 4 0 6 [0;11] 0 [0;0]
ALT increased _ALL Pembrolizumab 2 mg/kg Q3W
111 954 4 0 4 [0;8] 0 [0;0]
AST increased CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 48 19 13 [9;16] 5 [3;7]
AST increased CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 20 7 19 [11;28] 7 [2;12]
AST increased _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 68 26 14 [11;17] 5 [3;7]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
AST increased CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 1 0 0 [0;1] 0 [0;0]
AST increased CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 11 2 3 [1;5] 1 [0;1]
AST increased CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 2 0 4 [0;9] 0 [0;0]
AST increased KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 6 2 3 [1;5] 1 [0;2]
AST increased _ALL Ipilimumab 3 mg/kg Q3W 744 9964 20 4 2 [1;3] 0 [0;1]
AST increased CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 11 1 5 [2;8] 0 [0;1]
AST increased CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 2 1 1 [0;1] 0 [0;1]
AST increased CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 12 3 3 [1;5] 1 [0;2]
AST increased _ALL Nivolumab 3mg/kg Q2W 787 9604 25 5 3 [2;4] 1 [0;1]
AST increased KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 7 0 11 [3;19] 0 [0;0]
AST increased KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 14 0 6 [3;10] 0 [0;0]
AST increased _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 21 0 7 [4;11] 0 [0;0]
AST increased KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 5 2 8 [1;15] 3 [0;8]
AST increased KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
AST increased _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 7 2 5 [1;9] 2 [0;4]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
AST increased KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
AST increased KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 3 0 4 [0;9] 0 [0;0]
AST increased _ALL Pembrolizumab 2 mg/kg Q3W
111 954 4 0 4 [0;8] 0 [0;0]
Abdominal discomfort KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 2 0 3 [0;8] 0 [0;0]
Abdominal discomfort _ALL Pembrolizumab 10 mg/kg Q2W
57 627 2 0 3 [0;8] 0 [0;0]
Abdominal discomfort KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Abdominal discomfort KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 2 3 [0;7] 3 [0;7]
Abdominal discomfort _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 2 2 2 [0;4] 2 [0;4]
Abdominal discomfort KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Abdominal discomfort KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 2 2 3 [0;7] 3 [0;7]
Abdominal discomfort _ALL Pembrolizumab 2 mg/kg Q3W
111 954 2 2 2 [0;5] 2 [0;5]
Abdominal distension KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 3 1 5 [0;10] 2 [0;5]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Abdominal distension _ALL Pembrolizumab 10 mg/kg Q2W
57 627 3 1 5 [0;10] 2 [0;5]
Abdominal distension KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Abdominal distension _ALL Pembrolizumab 10 mg/kg Q3W
56 616 0 0 0 [0;0] 0 [0;0]
Abdominal distension KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Abdominal distension _ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Abdominal pain CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 10 0 10 [4;16] 0 [0;0]
Abdominal pain _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 10 0 10 [4;16] 0 [0;0]
Abdominal pain CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 20 2 5 [3;8] 1 [0;1]
Abdominal pain CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 4 1 8 [0;16] 2 [0;6]
Abdominal pain KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 15 0 7 [4;11] 0 [0;0]
Abdominal pain _ALL Ipilimumab 3 mg/kg Q3W 433 6170 39 3 6 [4;8] 0 [0;1]
Abdominal pain CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 8 0 2 [1;4] 0 [0;0]
Abdominal pain _ALL Nivolumab 3mg/kg Q2W 206 3440 8 0 2 [1;4] 0 [0;0]
Abdominal pain KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 6 1 10 [2;17] 2 [0;5]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Abdominal pain KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 10 0 5 [2;7] 0 [0;0]
Abdominal pain _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 16 1 6 [3;8] 0 [0;1]
Abdominal pain KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Abdominal pain KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 0 0 0 [0;0] 0 [0;0]
Abdominal pain _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 0 0 0 [0;0] 0 [0;0]
Abdominal pain KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
Abdominal pain KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 3 0 4 [0;9] 0 [0;0]
Abdominal pain _ALL Pembrolizumab 2 mg/kg Q3W
111 954 4 0 4 [0;8] 0 [0;0]
Abdominal pain upper KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Abdominal pain upper _ALL Ipilimumab 3 mg/kg Q3W 256 2022 1 0 0 [0;1] 0 [0;0]
Abdominal pain upper KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 4 0 2 [0;4] 0 [0;0]
Abdominal pain upper _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 4 0 2 [0;4] 0 [0;0]
Adrenal insufficiency CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 6 1 6 [1;10] 1 [0;3]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Adrenal insufficiency _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 6 1 6 [1;10] 1 [0;3]
Adrenal insufficiency CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 2 0 1 [0;1] 0 [0;0]
Adrenal insufficiency CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 2 1 4 [0;9] 2 [0;6]
Adrenal insufficiency _ALL Ipilimumab 3 mg/kg Q3W 177 4148 4 1 1 [0;2] 0 [0;1]
Alopecia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 2 0 1 [0;2] 0 [0;0]
Alopecia _ALL Ipilimumab 3 mg/kg Q3W 256 2022 2 0 1 [0;2] 0 [0;0]
Alopecia CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 1 0 0 [0;1] 0 [0;0]
Alopecia CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 7 0 2 [1;4] 0 [0;0]
Alopecia _ALL Nivolumab 3mg/kg Q2W 474 5691 8 0 1 [0;2] 0 [0;0]
Alopecia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 4 0 2 [0;4] 0 [0;0]
Alopecia _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 4 0 2 [0;4] 0 [0;0]
Alopecia KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 1 0 1 [0;2] 0 [0;0]
Alopecia _ALL Pembrolizumab 10 mg/kg Q3W
179 1790 1 0 1 [0;2] 0 [0;0]
Alopecia KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 5 0 3 [0;5] 0 [0;0]
Alopecia _ALL Pembrolizumab 2 mg/kg Q3W
178 1780 5 0 3 [0;5] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Anemia CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 15 4 4 [2;6] 1 [0;2]
Anemia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 1 0 [0;1] 0 [0;1]
Anemia _ALL Ipilimumab 3 mg/kg Q3W 387 5664 16 5 3 [1;4] 1 [0;2]
Anemia CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 10 2 4 [2;7] 1 [0;2]
Anemia CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 9 0 3 [1;4] 0 [0;0]
Anemia _ALL Nivolumab 3mg/kg Q2W 474 5691 19 2 3 [2;5] 0 [0;1]
Anemia KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 4 0 6 [0;13] 0 [0;0]
Anemia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 2 1 [0;3] 1 [0;2]
Anemia _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 7 2 2 [1;4] 1 [0;2]
Anemia KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Anemia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 1 0 1 [0;4] 0 [0;0]
Anemia KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 7 0 4 [1;7] 0 [0;0]
Anemia _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 8 0 3 [1;4] 0 [0;0]
Anemia KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Anemia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 3 1 4 [0;9] 1 [0;4]
Anemia KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 5 1 3 [0;5] 1 [0;2]
Anemia _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 8 2 3 [1;5] 1 [0;2]
Arthralgia CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 33 1 9 [6;12] 0 [0;1]
Arthralgia CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 10 0 10 [4;16] 0 [0;0]
Arthralgia _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 43 1 9 [6;12] 0 [0;1]
Arthralgia CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 19 0 5 [3;7] 0 [0;0]
Arthralgia CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 4 0 8 [0;16] 0 [0;0]
Arthralgia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 13 2 6 [3;10] 1 [0;2]
Arthralgia _ALL Ipilimumab 3 mg/kg Q3W 613 6323 36 2 6 [4;8] 0 [0;1]
Arthralgia CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 14 0 6 [3;9] 0 [0;0]
Arthralgia CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 12 0 3 [2;5] 0 [0;0]
Arthralgia CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 24 0 6 [4;9] 0 [0;0]
Arthralgia _ALL Nivolumab 3mg/kg Q2W 787 9604 50 0 5 [4;7] 0 [0;0]
Arthralgia KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 12 0 19 [8;30] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Arthralgia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 26 0 12 [7;16] 0 [0;0]
Arthralgia _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 38 0 13 [9;18] 0 [0;0]
Arthralgia KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 7 0 11 [3;20] 0 [0;0]
Arthralgia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 10 0 15 [6;24] 0 [0;0]
Arthralgia KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 11 1 6 [3;10] 1 [0;2]
Arthralgia _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 28 1 9 [6;12] 0 [0;1]
Arthralgia KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
Arthralgia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 11 0 15 [6;25] 0 [0;0]
Arthralgia KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 13 1 7 [3;11] 1 [0;2]
Arthralgia _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 25 1 9 [6;13] 0 [0;1]
Arthritis KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Arthritis _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
Arthritis KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 2 0 3 [0;8] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Arthritis KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 5 0 2 [0;4] 0 [0;0]
Arthritis _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 7 0 2 [1;4] 0 [0;0]
Arthritis KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Arthritis _ALL Pembrolizumab 10 mg/kg Q3W
56 616 0 0 0 [0;0] 0 [0;0]
Arthritis KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Arthritis _ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Asthenia CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 8 0 8 [2;13] 0 [0;0]
Asthenia _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 8 0 8 [2;13] 0 [0;0]
Asthenia CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 5 0 10 [1;19] 0 [0;0]
Asthenia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 16 2 8 [4;12] 1 [0;2]
Asthenia _ALL Ipilimumab 3 mg/kg Q3W 302 2528 21 2 8 [5;12] 1 [0;2]
Asthenia CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 21 0 6 [3;9] 0 [0;0]
Asthenia _ALL Nivolumab 3mg/kg Q2W 206 3440 21 0 6 [3;9] 0 [0;0]
Asthenia KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 11 0 18 [7;28] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Asthenia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 32 1 15 [10;20] 0 [0;1]
Asthenia _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 43 1 15 [11;20] 0 [0;1]
Asthenia KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 2 0 3 [0;8] 0 [0;0]
Asthenia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 6 0 9 [2;16] 0 [0;0]
Asthenia KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 8 1 4 [1;8] 1 [0;2]
Asthenia _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 16 1 5 [3;8] 0 [0;1]
Asthenia KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Asthenia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 5 0 7 [1;13] 0 [0;0]
Asthenia KEYNOTE-002 Pembrolizumab Pembrolizumab 2 mg/kg Q3W
178 median 1780 6 1 3 [1;6] 1 [0;2]
Asthenia _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 11 1 4 [2;6] 0 [0;1]
Back pain KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Back pain _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Back pain KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 2 0 3 [0;8] 0 [0;0]
Back pain KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 7 0 3 [1;6] 0 [0;0]
Back pain _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 9 0 3 [1;5] 0 [0;0]
Back pain KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Back pain KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Back pain _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 2 0 2 [0;4] 0 [0;0]
Back pain KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Back pain KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 3 0 4 [0;9] 0 [0;0]
Back pain _ALL Pembrolizumab 2 mg/kg Q3W
111 954 3 0 3 [0;7] 0 [0;0]
Balance disorder KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 2 0 3 [0;8] 0 [0;0]
Balance disorder _ALL Pembrolizumab 10 mg/kg Q2W
57 627 2 0 3 [0;8] 0 [0;0]
Balance disorder KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Balance disorder _ALL Pembrolizumab 10 mg/kg Q3W
56 616 0 0 0 [0;0] 0 [0;0]
Balance disorder KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Balance disorder _ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Blood TSH decreased CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 5 0 5 [1;9] 0 [0;0]
Blood TSH decreased _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 5 0 5 [1;9] 0 [0;0]
Blood TSH decreased CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 0 0 0 [0;0] 0 [0;0]
Blood TSH decreased KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 2 1 1 [0;2] 0 [0;1]
Blood TSH decreased _ALL Ipilimumab 3 mg/kg Q3W 302 2528 2 1 1 [0;2] 0 [0;1]
Blood TSH decreased CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 3 0 1 [0;3] 0 [0;0]
Blood TSH decreased _ALL Nivolumab 3mg/kg Q2W 268 2251 3 0 1 [0;3] 0 [0;0]
Blood TSH decreased KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
Blood TSH decreased _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 3 0 1 [0;3] 0 [0;0]
Blood TSH decreased KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Blood TSH decreased _ALL Pembrolizumab 10 mg/kg Q3W
84 672 2 0 3 [0;7] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Blood TSH decreased KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 0 0 0 [0;0] 0 [0;0]
Blood TSH decreased _ALL Pembrolizumab 2 mg/kg Q3W
89 712 0 0 0 [0;0] 0 [0;0]
Blood TSH increased CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 1 0 0 [0;1] 0 [0;0]
Blood TSH increased KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Blood TSH increased _ALL Ipilimumab 3 mg/kg Q3W 387 5664 2 0 0 [0;1] 0 [0;0]
Blood TSH increased KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 2 0 1 [0;2] 0 [0;0]
Blood TSH increased _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 2 0 1 [0;2] 0 [0;0]
Blood TSH increased KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 3 0 4 [0;10] 0 [0;0]
Blood TSH increased _ALL Pembrolizumab 10 mg/kg Q3W
84 672 3 0 4 [0;10] 0 [0;0]
Blood TSH increased KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 1 0 1 [0;4] 0 [0;0]
Blood TSH increased _ALL Pembrolizumab 2 mg/kg Q3W
89 712 1 0 1 [0;4] 0 [0;0]
Blood alkaline phosphatase increased
KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 4 0 2 [0;4] 0 [0;0]
Blood alkaline phosphatase increased
_ALL Ipilimumab 3 mg/kg Q3W 256 2022 4 0 2 [0;4] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Blood alkaline phosphatase increased
KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 2 0 3 [0;8] 0 [0;0]
Blood alkaline phosphatase increased
KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 2 0 1 [0;2] 0 [0;0]
Blood alkaline phosphatase increased
_ALL Pembrolizumab 10 mg/kg Q2W
335 2823 4 0 1 [0;3] 0 [0;0]
Blood alkaline phosphatase increased
KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Blood alkaline phosphatase increased
_ALL Pembrolizumab 10 mg/kg Q3W
56 616 0 0 0 [0;0] 0 [0;0]
Blood alkaline phosphatase increased
KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Blood alkaline phosphatase increased
_ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Blood bilirubin increased CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 5 0 5 [1;9] 0 [0;0]
Blood bilirubin increased _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 5 0 5 [1;9] 0 [0;0]
Blood bilirubin increased CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 0 0 0 [0;0] 0 [0;0]
Blood bilirubin increased KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Blood bilirubin increased _ALL Ipilimumab 3 mg/kg Q3W 302 2528 0 0 0 [0;0] 0 [0;0]
Blood bilirubin increased CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 2 0 1 [0;1] 0 [0;0]
Blood bilirubin increased _ALL Nivolumab 3mg/kg Q2W 206 3440 2 0 1 [0;1] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Blood bilirubin increased KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 6 0 3 [1;5] 0 [0;0]
Blood bilirubin increased _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 6 0 3 [1;5] 0 [0;0]
Blood cholesterol increased
KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 2 0 3 [0;8] 0 [0;0]
Blood cholesterol increased
_ALL Pembrolizumab 10 mg/kg Q2W
57 627 2 0 3 [0;8] 0 [0;0]
Blood cholesterol increased
KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Blood cholesterol increased
_ALL Pembrolizumab 10 mg/kg Q3W
56 616 0 0 0 [0;0] 0 [0;0]
Blood cholesterol increased
KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Blood cholesterol increased
_ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Blood creatinine increased CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 2 1 2 [0;5] 1 [0;3]
Blood creatinine increased _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 2 1 2 [0;5] 1 [0;3]
Blood creatinine increased CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 0 0 0 [0;0] 0 [0;0]
Blood creatinine increased KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Blood creatinine increased _ALL Ipilimumab 3 mg/kg Q3W 302 2528 1 0 0 [0;1] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Blood creatinine increased CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 2 0 1 [0;2] 0 [0;0]
Blood creatinine increased CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 1 0 0 [0;1] 0 [0;0]
Blood creatinine increased _ALL Nivolumab 3mg/kg Q2W 474 5691 3 0 1 [0;1] 0 [0;0]
Blood creatinine increased KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 3 0 5 [0;10] 0 [0;0]
Blood creatinine increased KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 4 0 2 [0;4] 0 [0;0]
Blood creatinine increased _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 7 0 2 [1;4] 0 [0;0]
Blood creatinine increased KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Blood creatinine increased _ALL Pembrolizumab 10 mg/kg Q3W
56 616 0 0 0 [0;0] 0 [0;0]
Blood creatinine increased KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Blood creatinine increased _ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Blood lactate dehydrogenase increased
KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Blood lactate dehydrogenase increased
_ALL Ipilimumab 3 mg/kg Q3W 256 2022 1 0 0 [0;1] 0 [0;0]
Blood lactate dehydrogenase increased
KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 5 1 2 [0;4] 0 [0;1]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Blood lactate dehydrogenase increased
_ALL Pembrolizumab 10 mg/kg Q2W
278 2196 5 1 2 [0;4] 0 [0;1]
Bone pain KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Bone pain _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
Bone pain KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
Bone pain _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 3 0 1 [0;3] 0 [0;0]
Chest pain KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Chest pain _ALL Pembrolizumab 10 mg/kg Q3W
84 672 2 0 3 [0;7] 0 [0;0]
Chest pain KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 0 0 0 [0;0] 0 [0;0]
Chest pain _ALL Pembrolizumab 2 mg/kg Q3W
89 712 0 0 0 [0;0] 0 [0;0]
Chills CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 10 0 10 [4;16] 0 [0;0]
Chills _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 10 0 10 [4;16] 0 [0;0]
Chills CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 3 0 6 [0;13] 0 [0;0]
Chills KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 2 0 1 [0;2] 0 [0;0]
Chills _ALL Ipilimumab 3 mg/kg Q3W 302 2528 5 0 2 [0;4] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Chills KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 6 0 10 [2;17] 0 [0;0]
Chills KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
Chills _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 9 0 3 [1;5] 0 [0;0]
Chills KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 2 0 3 [0;8] 0 [0;0]
Chills KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 3 0 4 [0;10] 0 [0;0]
Chills _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 5 0 4 [0;7] 0 [0;0]
Chills KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
Chills KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 7 0 10 [3;17] 0 [0;0]
Chills _ALL Pembrolizumab 2 mg/kg Q3W
111 954 8 0 8 [3;14] 0 [0;0]
Colitis CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 37 24 10 [7;13] 6 [4;9]
Colitis CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 22 16 21 [12;30] 15 [8;23]
Colitis _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 59 40 12 [9;15] 8 [6;11]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Colitis CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 10 7 3 [1;4] 2 [0;3]
Colitis CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 36 27 9 [6;13] 7 [4;10]
Colitis CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 6 3 12 [2;21] 6 [0;13]
Colitis KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 19 16 9 [5;14] 8 [4;12]
Colitis _ALL Ipilimumab 3 mg/kg Q3W 744 9964 71 53 7 [5;9] 5 [4;7]
Colitis CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 3 2 1 [0;3] 1 [0;2]
Colitis CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 2 1 1 [0;1] 0 [0;1]
Colitis CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 4 2 1 [0;2] 1 [0;1]
Colitis _ALL Nivolumab 3mg/kg Q2W 787 9604 9 5 1 [0;2] 1 [0;1]
Colitis KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 4 4 2 [0;4] 2 [0;4]
Colitis _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 4 4 2 [0;4] 2 [0;4]
Confusion KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 1 0 2 [0;5] 0 [0;0]
Confusion _ALL Pembrolizumab 10 mg/kg Q2W
57 627 1 0 2 [0;5] 0 [0;0]
Confusion KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
Confusion _ALL Pembrolizumab 10 mg/kg Q3W
56 616 1 0 2 [0;5] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Confusion KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Confusion _ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Conjunctivitis KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Conjunctivitis _ALL Ipilimumab 3 mg/kg Q3W 256 2022 1 0 0 [0;1] 0 [0;0]
Conjunctivitis KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 4 0 2 [0;4] 0 [0;0]
Conjunctivitis _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 4 0 2 [0;4] 0 [0;0]
Constipation CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 10 1 10 [4;16] 1 [0;3]
Constipation _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 10 1 10 [4;16] 1 [0;3]
Constipation CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 27 3 7 [5;10] 1 [0;2]
Constipation CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 4 0 8 [0;16] 0 [0;0]
Constipation KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 5 0 2 [0;5] 0 [0;0]
Constipation _ALL Ipilimumab 3 mg/kg Q3W 433 6170 36 3 6 [4;8] 0 [0;1]
Constipation CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 6 0 3 [1;5] 0 [0;0]
Constipation CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 22 0 6 [4;9] 0 [0;0]
Constipation _ALL Nivolumab 3mg/kg Q2W 474 5691 28 0 5 [3;7] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Constipation KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 2 0 3 [0;8] 0 [0;0]
Constipation KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 7 0 3 [1;6] 0 [0;0]
Constipation _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 9 0 3 [1;5] 0 [0;0]
Constipation KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 2 0 3 [0;8] 0 [0;0]
Constipation KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 4 0 6 [0;12] 0 [0;0]
Constipation KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 9 0 5 [2;8] 0 [0;0]
Constipation _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 15 0 5 [2;7] 0 [0;0]
Constipation KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Constipation KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 4 0 6 [0;11] 0 [0;0]
Constipation KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 5 0 3 [0;5] 0 [0;0]
Constipation _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 9 0 3 [1;5] 0 [0;0]
Cough CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 21 0 6 [3;8] 0 [0;0]
Cough KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Cough _ALL Ipilimumab 3 mg/kg Q3W 387 5664 21 0 4 [2;5] 0 [0;0]
Cough CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 6 0 2 [0;3] 0 [0;0]
Cough _ALL Nivolumab 3mg/kg Q2W 206 3440 6 0 2 [0;3] 0 [0;0]
Cough KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 6 0 10 [2;17] 0 [0;0]
Cough KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 10 0 5 [2;7] 0 [0;0]
Cough _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 16 0 6 [3;8] 0 [0;0]
Cough KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 3 0 5 [0;10] 0 [0;0]
Cough KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 6 0 9 [2;16] 0 [0;0]
Cough _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 9 0 7 [2;12] 0 [0;0]
Cough KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 2 0 8 [0;20] 0 [0;0]
Cough KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 8 0 11 [3;19] 0 [0;0]
Cough _ALL Pembrolizumab 2 mg/kg Q3W
111 954 10 0 10 [4;17] 0 [0;0]
Decrease in serum corticotropin
CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 2 0 1 [0;1] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Decrease in serum corticotropin
_ALL Ipilimumab 3 mg/kg Q3W 131 3642 2 0 1 [0;1] 0 [0;0]
Decreased appetite CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 56 4 15 [11;19] 1 [0;2]
Decreased appetite CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 14 0 14 [6;21] 0 [0;0]
Decreased appetite _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 70 4 14 [11;18] 1 [0;2]
Decreased appetite CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 35 2 10 [6;13] 1 [0;1]
Decreased appetite CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 39 1 10 [7;14] 0 [0;1]
Decreased appetite CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 4 0 8 [0;16] 0 [0;0]
Decreased appetite KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 20 0 10 [6;14] 0 [0;0]
Decreased appetite _ALL Ipilimumab 3 mg/kg Q3W 744 9964 98 3 10 [8;12] 0 [0;1]
Decreased appetite CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 14 0 6 [3;9] 0 [0;0]
Decreased appetite CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 11 0 3 [1;5] 0 [0;0]
Decreased appetite CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 34 0 9 [6;12] 0 [0;0]
Decreased appetite _ALL Nivolumab 3mg/kg Q2W 787 9604 59 0 6 [5;8] 0 [0;0]
Decreased appetite KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 5 1 8 [1;15] 2 [0;5]
Decreased appetite KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 17 0 8 [4;11] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Decreased appetite _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 22 1 8 [5;11] 0 [0;1]
Decreased appetite KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Decreased appetite KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 5 0 7 [1;14] 0 [0;0]
Decreased appetite KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 17 2 9 [5;14] 1 [0;3]
Decreased appetite _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 22 2 7 [4;10] 1 [0;2]
Decreased appetite KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
Decreased appetite KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 8 0 11 [3;19] 0 [0;0]
Decreased appetite KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 8 0 4 [1;8] 0 [0;0]
Decreased appetite _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 17 0 6 [3;9] 0 [0;0]
Dehydration KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 2 0 3 [0;8] 0 [0;0]
Dehydration _ALL Pembrolizumab 10 mg/kg Q2W
57 627 2 0 3 [0;8] 0 [0;0]
Dehydration KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Dehydration KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 1 0 1 [0;4] 0 [0;0]
Dehydration _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 1 0 1 [0;2] 0 [0;0]
Dehydration KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Dehydration KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 1 0 1 [0;4] 0 [0;0]
Dehydration _ALL Pembrolizumab 2 mg/kg Q3W
111 954 1 0 1 [0;3] 0 [0;0]
Dermatitis KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Dermatitis _ALL Ipilimumab 3 mg/kg Q3W 256 2022 1 0 0 [0;1] 0 [0;0]
Dermatitis CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 5 0 2 [0;4] 0 [0;0]
Dermatitis _ALL Nivolumab 3mg/kg Q2W 268 2251 5 0 2 [0;4] 0 [0;0]
Dermatitis KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
Dermatitis _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 3 0 1 [0;3] 0 [0;0]
Diabetes mellitus CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 1 0 0 [0;1] 0 [0;0]
Diabetes mellitus _ALL Nivolumab 3mg/kg Q2W 206 3440 1 0 0 [0;1] 0 [0;0]
Diarrhea CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 138 29 36 [30;42] 8 [5;10]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Diarrhea CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 42 10 41 [28;53] 10 [4;16]
Diarrhea _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 180 39 37 [32;43] 8 [6;11]
Diarrhea CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 43 7 12 [8;15] 2 [0;3]
Diarrhea CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 103 19 27 [22;32] 5 [3;7]
Diarrhea CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 17 5 34 [18;50] 10 [1;19]
Diarrhea KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 58 8 29 [21;36] 4 [1;7]
Diarrhea _ALL Ipilimumab 3 mg/kg Q3W 744 9964 221 39 22 [19;25] 4 [3;5]
Diarrhea CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 30 1 13 [9;18] 0 [0;1]
Diarrhea CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 33 2 10 [6;13] 1 [0;1]
Diarrhea CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 60 7 15 [11;19] 2 [0;3]
Diarrhea _ALL Nivolumab 3mg/kg Q2W 787 9604 123 10 13 [11;15] 1 [0;2]
Diarrhea KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 12 1 19 [8;30] 2 [0;5]
Diarrhea KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 47 7 21 [15;28] 3 [1;6]
Diarrhea _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 59 8 21 [16;26] 3 [1;5]
Diarrhea KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 9 0 15 [5;24] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Diarrhea KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 12 1 18 [8;28] 1 [0;4]
Diarrhea KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 19 2 11 [6;15] 1 [0;3]
Diarrhea _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 40 3 13 [9;17] 1 [0;2]
Diarrhea KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 6 0 25 [5;45] 0 [0;0]
Diarrhea KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 10 0 14 [5;23] 0 [0;0]
Diarrhea KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 15 0 8 [4;13] 0 [0;0]
Diarrhea _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 31 0 11 [7;15] 0 [0;0]
Diverticulitis KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 1 0 2 [0;5] 0 [0;0]
Diverticulitis _ALL Pembrolizumab 10 mg/kg Q2W
57 627 1 0 2 [0;5] 0 [0;0]
Diverticulitis KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
Diverticulitis _ALL Pembrolizumab 10 mg/kg Q3W
56 616 1 0 2 [0;5] 0 [0;0]
Diverticulitis KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Diverticulitis _ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Dizziness KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 2 0 1 [0;2] 0 [0;0]
Dizziness _ALL Ipilimumab 3 mg/kg Q3W 256 2022 2 0 1 [0;2] 0 [0;0]
Dizziness KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 2 0 3 [0;8] 0 [0;0]
Dizziness KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 8 0 4 [1;6] 0 [0;0]
Dizziness _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 10 0 4 [1;6] 0 [0;0]
Dizziness KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
Dizziness KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 0 0 0 [0;0] 0 [0;0]
Dizziness _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 1 0 1 [0;2] 0 [0;0]
Dizziness KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Dizziness KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 2 0 3 [0;7] 0 [0;0]
Dizziness _ALL Pembrolizumab 2 mg/kg Q3W
111 954 2 0 2 [0;5] 0 [0;0]
Dry eye KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 4 0 6 [0;13] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Dry eye _ALL Pembrolizumab 10 mg/kg Q2W
57 627 4 0 6 [0;13] 0 [0;0]
Dry eye KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Dry eye KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 0 0 0 [0;0] 0 [0;0]
Dry eye _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 0 0 0 [0;0] 0 [0;0]
Dry eye KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Dry eye KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 2 0 3 [0;7] 0 [0;0]
Dry eye _ALL Pembrolizumab 2 mg/kg Q3W
111 954 2 0 2 [0;5] 0 [0;0]
Dry mouth KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Dry mouth _ALL Ipilimumab 3 mg/kg Q3W 256 2022 1 0 0 [0;1] 0 [0;0]
Dry mouth KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 3 0 5 [0;10] 0 [0;0]
Dry mouth KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 20 0 9 [5;13] 0 [0;0]
Dry mouth _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 23 0 8 [5;11] 0 [0;0]
Dry mouth KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Dry mouth KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Dry mouth _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 3 0 2 [0;5] 0 [0;0]
Dry mouth KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Dry mouth KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 0 0 0 [0;0] 0 [0;0]
Dry mouth _ALL Pembrolizumab 2 mg/kg Q3W
111 954 0 0 0 [0;0] 0 [0;0]
Dry skin KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 3 0 1 [0;3] 0 [0;0]
Dry skin _ALL Ipilimumab 3 mg/kg Q3W 256 2022 3 0 1 [0;3] 0 [0;0]
Dry skin CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 9 0 3 [1;4] 0 [0;0]
Dry skin _ALL Nivolumab 3mg/kg Q2W 206 3440 9 0 3 [1;4] 0 [0;0]
Dry skin KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 6 0 3 [1;5] 0 [0;0]
Dry skin _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 6 0 3 [1;5] 0 [0;0]
Dry skin KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 0 0 0 [0;0] 0 [0;0]
Dry skin KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 9 0 5 [2;8] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Dry skin _ALL Pembrolizumab 10 mg/kg Q3W
263 2462 9 0 4 [1;6] 0 [0;0]
Dry skin KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 2 0 3 [0;7] 0 [0;0]
Dry skin KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 9 0 5 [2;8] 0 [0;0]
Dry skin _ALL Pembrolizumab 2 mg/kg Q3W
267 2492 11 0 4 [2;7] 0 [0;0]
Dysgueusia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 3 0 1 [0;3] 0 [0;0]
Dysgueusia _ALL Ipilimumab 3 mg/kg Q3W 256 2022 3 0 1 [0;3] 0 [0;0]
Dysgueusia CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 6 0 2 [0;3] 0 [0;0]
Dysgueusia _ALL Nivolumab 3mg/kg Q2W 206 3440 6 0 2 [0;3] 0 [0;0]
Dysgueusia KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 0 0 0 [0;0] 0 [0;0]
Dysgueusia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 10 0 5 [2;7] 0 [0;0]
Dysgueusia _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 10 0 4 [1;6] 0 [0;0]
Dysgueusia KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
Dysgueusia _ALL Pembrolizumab 10 mg/kg Q3W
56 616 1 0 2 [0;5] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Dysgueusia KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
Dysgueusia _ALL Pembrolizumab 2 mg/kg Q3W
22 242 1 0 4 [0;12] 0 [0;0]
Dyspepsia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Dyspepsia _ALL Ipilimumab 3 mg/kg Q3W 256 2022 1 0 0 [0;1] 0 [0;0]
Dyspepsia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 4 0 2 [0;4] 0 [0;0]
Dyspepsia _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 4 0 2 [0;4] 0 [0;0]
Dyspnea CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 32 2 8 [5;11] 1 [0;1]
Dyspnea CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 9 3 9 [3;14] 3 [0;6]
Dyspnea _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 41 5 8 [6;11] 1 [0;2]
Dyspnea CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 19 5 5 [3;8] 1 [0;3]
Dyspnea CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 13 0 3 [2;5] 0 [0;0]
Dyspnea CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 5 0 10 [1;19] 0 [0;0]
Dyspnea KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 3 1 1 [0;3] 0 [0;1]
Dyspnea _ALL Ipilimumab 3 mg/kg Q3W 744 9964 40 6 4 [3;5] 1 [0;1]
Dyspnea CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 14 1 4 [2;5] 0 [0;1]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Dyspnea _ALL Nivolumab 3mg/kg Q2W 313 3913 14 1 4 [2;5] 0 [0;1]
Dyspnea KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 5 0 8 [1;15] 0 [0;0]
Dyspnea KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 4 0 2 [0;4] 0 [0;0]
Dyspnea _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 9 0 3 [1;5] 0 [0;0]
Dyspnea KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Dyspnea KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 7 1 10 [3;18] 1 [0;4]
Dyspnea _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 7 1 5 [1;9] 1 [0;2]
Dyspnea KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
Dyspnea KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 7 0 10 [3;17] 0 [0;0]
Dyspnea _ALL Pembrolizumab 2 mg/kg Q3W
111 954 8 0 8 [3;14] 0 [0;0]
Dyspnea exertional KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 1 0 1 [0;4] 0 [0;0]
Dyspnea exertional _ALL Pembrolizumab 10 mg/kg Q3W
84 672 1 0 1 [0;4] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Dyspnea exertional KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 1 0 1 [0;4] 0 [0;0]
Dyspnea exertional _ALL Pembrolizumab 2 mg/kg Q3W
89 712 1 0 1 [0;4] 0 [0;0]
Eczema KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Eczema _ALL Ipilimumab 3 mg/kg Q3W 256 2022 1 0 0 [0;1] 0 [0;0]
Eczema CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 5 0 1 [0;3] 0 [0;0]
Eczema _ALL Nivolumab 3mg/kg Q2W 206 3440 5 0 1 [0;3] 0 [0;0]
Eczema KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 3 0 5 [0;10] 0 [0;0]
Eczema KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 4 0 2 [0;4] 0 [0;0]
Eczema _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 7 0 2 [1;4] 0 [0;0]
Eczema KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Eczema _ALL Pembrolizumab 10 mg/kg Q3W
56 616 0 0 0 [0;0] 0 [0;0]
Eczema KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Eczema _ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Eosinophilia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 2 0 1 [0;2] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Eosinophilia _ALL Ipilimumab 3 mg/kg Q3W 256 2022 2 0 1 [0;2] 0 [0;0]
Eosinophilia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 0 0 0 [0;0] 0 [0;0]
Eosinophilia _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 0 0 0 [0;0] 0 [0;0]
Erythema CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 6 0 6 [1;10] 0 [0;0]
Erythema _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 6 0 6 [1;10] 0 [0;0]
Erythema CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 0 0 0 [0;0] 0 [0;0]
Erythema KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 5 0 2 [0;5] 0 [0;0]
Erythema _ALL Ipilimumab 3 mg/kg Q3W 302 2528 5 0 2 [0;4] 0 [0;0]
Erythema CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 13 0 4 [2;6] 0 [0;0]
Erythema _ALL Nivolumab 3mg/kg Q2W 206 3440 13 0 4 [2;6] 0 [0;0]
Erythema KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 1 0 2 [0;5] 0 [0;0]
Erythema KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 8 0 4 [1;6] 0 [0;0]
Erythema _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 9 0 3 [1;5] 0 [0;0]
Erythema KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Erythema KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Erythema _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 2 0 2 [0;4] 0 [0;0]
Erythema KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
Erythema KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 4 0 6 [0;11] 0 [0;0]
Erythema _ALL Pembrolizumab 2 mg/kg Q3W
111 954 5 0 5 [1;10] 0 [0;0]
Face oedema KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 1 0 1 [0;4] 0 [0;0]
Face oedema _ALL Pembrolizumab 10 mg/kg Q3W
84 672 1 0 1 [0;4] 0 [0;0]
Face oedema KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 2 0 3 [0;7] 0 [0;0]
Face oedema _ALL Pembrolizumab 2 mg/kg Q3W
89 712 2 0 3 [0;7] 0 [0;0]
Fatigue CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 110 13 29 [23;34] 3 [2;5]
Fatigue CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 37 5 36 [24;47] 5 [1;9]
Fatigue _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 147 18 30 [25;35] 4 [2;5]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Fatigue CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 55 9 15 [11;19] 2 [1;4]
Fatigue CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 87 3 23 [18;28] 1 [0;2]
Fatigue CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 20 0 40 [22;57] 0 [0;0]
Fatigue KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 39 3 19 [13;25] 1 [0;3]
Fatigue _ALL Ipilimumab 3 mg/kg Q3W 744 9964 201 15 20 [17;23] 2 [1;2]
Fatigue CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 65 2 29 [22;36] 1 [0;2]
Fatigue CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 41 0 12 [8;16] 0 [0;0]
Fatigue CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 107 4 27 [22;33] 1 [0;2]
Fatigue _ALL Nivolumab 3mg/kg Q2W 787 9604 213 6 22 [19;25] 1 [0;1]
Fatigue KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 26 2 41 [26;57] 3 [0;8]
Fatigue KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 58 0 26 [20;33] 0 [0;0]
Fatigue _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 84 2 30 [23;36] 1 [0;2]
Fatigue KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 13 0 21 [10;33] 0 [0;0]
Fatigue KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 31 0 46 [30;62] 0 [0;0]
Fatigue KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 52 1 29 [21;37] 1 [0;2]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Fatigue _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 96 1 31 [25;37] 0 [0;1]
Fatigue KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 2 0 8 [0;20] 0 [0;0]
Fatigue KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 29 5 41 [26;56] 7 [1;13]
Fatigue KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 40 2 22 [16;29] 1 [0;3]
Fatigue _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 71 7 26 [20;32] 3 [1;4]
Flatulence KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 4 0 2 [0;4] 0 [0;0]
Flatulence _ALL Ipilimumab 3 mg/kg Q3W 256 2022 4 0 2 [0;4] 0 [0;0]
Flatulence KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 1 0 0 [0;1] 0 [0;0]
Flatulence _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 1 0 0 [0;1] 0 [0;0]
Flushing KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 2 0 1 [0;2] 0 [0;0]
Flushing _ALL Ipilimumab 3 mg/kg Q3W 256 2022 2 0 1 [0;2] 0 [0;0]
Flushing CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 1 0 0 [0;1] 0 [0;0]
Flushing _ALL Nivolumab 3mg/kg Q2W 206 3440 1 0 0 [0;1] 0 [0;0]
Flushing KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Flushing _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 3 0 1 [0;3] 0 [0;0]
Frequent bowel movements
KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Frequent bowel movements
_ALL Ipilimumab 3 mg/kg Q3W 256 2022 1 0 0 [0;1] 0 [0;0]
Frequent bowel movements
CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 2 0 1 [0;1] 0 [0;0]
Frequent bowel movements
_ALL Nivolumab 3mg/kg Q2W 206 3440 2 0 1 [0;1] 0 [0;0]
Frequent bowel movements
KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 0 0 0 [0;0] 0 [0;0]
Frequent bowel movements
_ALL Pembrolizumab 10 mg/kg Q2W
278 2196 0 0 0 [0;0] 0 [0;0]
Gastro-oesophageal reflux KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 0 0 0 [0;0] 0 [0;0]
Gastro-oesophageal reflux _ALL Pembrolizumab 10 mg/kg Q3W
84 672 0 0 0 [0;0] 0 [0;0]
Gastro-oesophageal reflux KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 3 0 4 [0;9] 0 [0;0]
Gastro-oesophageal reflux _ALL Pembrolizumab 2 mg/kg Q3W
89 712 3 0 4 [0;9] 0 [0;0]
Hair color changes KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Hair color changes _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Hair color changes KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 2 0 3 [0;8] 0 [0;0]
Hair color changes KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 4 0 2 [0;4] 0 [0;0]
Hair color changes _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 6 0 2 [0;4] 0 [0;0]
Hair color changes KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Hair color changes _ALL Pembrolizumab 10 mg/kg Q3W
56 616 0 0 0 [0;0] 0 [0;0]
Hair color changes KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Hair color changes _ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Headache CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 32 1 8 [5;11] 0 [0;1]
Headache CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 13 2 13 [6;19] 2 [0;5]
Headache _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 45 3 9 [7;12] 1 [0;1]
Headache CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 19 3 5 [3;8] 1 [0;2]
Headache CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 13 0 3 [2;5] 0 [0;0]
Headache CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 5 0 10 [1;19] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Headache KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 9 0 4 [2;7] 0 [0;0]
Headache _ALL Ipilimumab 3 mg/kg Q3W 744 9964 46 3 5 [3;6] 0 [0;1]
Headache CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 9 0 3 [1;4] 0 [0;0]
Headache CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 23 0 6 [3;8] 0 [0;0]
Headache _ALL Nivolumab 3mg/kg Q2W 519 7353 32 0 4 [3;6] 0 [0;0]
Headache KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 10 0 16 [6;26] 0 [0;0]
Headache KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 9 0 4 [1;7] 0 [0;0]
Headache _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 19 0 7 [4;10] 0 [0;0]
Headache KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 3 0 5 [0;10] 0 [0;0]
Headache KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 3 0 4 [0;10] 0 [0;0]
Headache _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 6 0 5 [1;8] 0 [0;0]
Headache KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
Headache KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 4 0 6 [0;11] 0 [0;0]
Headache _ALL Pembrolizumab 2 mg/kg Q3W
111 954 5 0 5 [1;10] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Hepatitis CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 3 3 3 [0;6] 3 [0;6]
Hepatitis _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 3 3 3 [0;6] 3 [0;6]
Hepatitis CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 1 0 0 [0;1] 0 [0;0]
Hepatitis CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 0 0 0 [0;0] 0 [0;0]
Hepatitis _ALL Ipilimumab 3 mg/kg Q3W 177 4148 1 0 0 [0;1] 0 [0;0]
Hepatocellular injury KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 3 2 1 [0;3] 1 [0;2]
Hepatocellular injury _ALL Ipilimumab 3 mg/kg Q3W 256 2022 3 2 1 [0;3] 1 [0;2]
Hepatocellular injury KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 0 0 0 [0;0] 0 [0;0]
Hepatocellular injury _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 0 0 0 [0;0] 0 [0;0]
Hot flush KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Hot flush _ALL Ipilimumab 3 mg/kg Q3W 256 2022 1 0 0 [0;1] 0 [0;0]
Hot flush CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 3 0 1 [0;2] 0 [0;0]
Hot flush _ALL Nivolumab 3mg/kg Q2W 206 3440 3 0 1 [0;2] 0 [0;0]
Hot flush KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 2 0 3 [0;8] 0 [0;0]
Hot flush KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Hot flush _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 5 0 2 [0;3] 0 [0;0]
Hot flush KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
Hot flush _ALL Pembrolizumab 10 mg/kg Q3W
56 616 1 0 2 [0;5] 0 [0;0]
Hot flush KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Hot flush _ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Hyperglycemia KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 1 0 2 [0;5] 0 [0;0]
Hyperglycemia _ALL Pembrolizumab 10 mg/kg Q2W
57 627 1 0 2 [0;5] 0 [0;0]
Hyperglycemia KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Hyperglycemia _ALL Pembrolizumab 10 mg/kg Q3W
56 616 0 0 0 [0;0] 0 [0;0]
Hyperglycemia KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
Hyperglycemia _ALL Pembrolizumab 2 mg/kg Q3W
22 242 1 0 4 [0;12] 0 [0;0]
Hyperhidrosis CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 2 0 1 [0;1] 0 [0;0]
Hyperhidrosis _ALL Nivolumab 3mg/kg Q2W 206 3440 2 0 1 [0;1] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Hypersensitivity KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 2 0 1 [0;2] 0 [0;0]
Hypersensitivity _ALL Ipilimumab 3 mg/kg Q3W 256 2022 2 0 1 [0;2] 0 [0;0]
Hypersensitivity CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 2 0 1 [0;2] 0 [0;0]
Hypersensitivity CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 6 0 2 [0;3] 0 [0;0]
Hypersensitivity _ALL Nivolumab 3mg/kg Q2W 474 5691 8 0 1 [0;2] 0 [0;0]
Hypersensitivity KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 2 0 1 [0;2] 0 [0;0]
Hypersensitivity _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 2 0 1 [0;2] 0 [0;0]
Hypertension KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Hypertension _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
Hypertension KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 2 1 [0;3] 1 [0;2]
Hypertension _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 3 2 1 [0;3] 1 [0;2]
Hyperthyroidism CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 31 3 8 [5;11] 1 [0;2]
Hyperthyroidism CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 4 0 4 [0;8] 0 [0;0]
Hyperthyroidism _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 35 3 7 [5;10] 1 [0;1]
Hyperthyroidism CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 3 0 1 [0;2] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Hyperthyroidism CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 0 0 0 [0;0] 0 [0;0]
Hyperthyroidism KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 6 1 3 [1;5] 0 [0;1]
Hyperthyroidism _ALL Ipilimumab 3 mg/kg Q3W 613 6323 9 1 1 [0;2] 0 [0;0]
Hyperthyroidism CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 5 0 2 [0;4] 0 [0;0]
Hyperthyroidism CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 7 1 2 [1;4] 0 [0;1]
Hyperthyroidism CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 13 . 3 [2;5] . [0;.]
Hyperthyroidism _ALL Nivolumab 3mg/kg Q2W 787 9604 25 1 3 [2;4] 0 [0;0]
Hyperthyroidism KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 17 0 8 [4;11] 0 [0;0]
Hyperthyroidism _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 17 0 8 [4;11] 0 [0;0]
Hyperthyroidism KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Hyperthyroidism _ALL Pembrolizumab 10 mg/kg Q3W
84 672 2 0 3 [0;7] 0 [0;0]
Hyperthyroidism KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 1 0 1 [0;4] 0 [0;0]
Hyperthyroidism _ALL Pembrolizumab 2 mg/kg Q3W
89 712 1 0 1 [0;4] 0 [0;0]
Hypertriglyceridemia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Hypertriglyceridemia _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Hypertriglyceridemia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 1 0 0 [0;1] 0 [0;0]
Hypertriglyceridemia _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 1 0 0 [0;1] 0 [0;0]
Hypocalcemia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Hypocalcemia _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
Hypocalcemia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 6 0 3 [1;5] 0 [0;0]
Hypocalcemia _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 6 0 3 [1;5] 0 [0;0]
Hypoesthesia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 0 0 0 [0;0] 0 [0;0]
Hypoesthesia _ALL Pembrolizumab 10 mg/kg Q3W
84 672 0 0 0 [0;0] 0 [0;0]
Hypoesthesia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 3 0 4 [0;9] 0 [0;0]
Hypoesthesia _ALL Pembrolizumab 2 mg/kg Q3W
89 712 3 0 4 [0;9] 0 [0;0]
Hypomagnesemia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Hypomagnesemia _ALL Ipilimumab 3 mg/kg Q3W 256 2022 1 0 0 [0;1] 0 [0;0]
Hypomagnesemia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 2 0 1 [0;2] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Hypomagnesemia _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 2 0 1 [0;2] 0 [0;0]
Hypophysitis CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 24 5 6 [4;9] 1 [0;2]
Hypophysitis _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 3819 24 5 6 [4;9] 1 [0;2]
Hypophysitis CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 2 2 1 [0;1] 1 [0;1]
Hypophysitis CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 12 6 3 [1;5] 2 [0;3]
Hypophysitis CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 3 2 6 [0;13] 4 [0;9]
Hypophysitis KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 4 2 2 [0;4] 1 [0;2]
Hypophysitis _ALL Ipilimumab 3 mg/kg Q3W 744 9964 21 12 2 [1;3] 1 [1;2]
Hypophysitis CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 1 1 0 [0;1] 0 [0;1]
Hypophysitis CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 2 1 1 [0;1] 0 [0;1]
Hypophysitis _ALL Nivolumab 3mg/kg Q2W 519 7353 3 2 0 [0;1] 0 [0;1]
Hypophysitis KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 0 0 0 [0;0] 0 [0;0]
Hypophysitis _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 0 0 0 [0;0] 0 [0;0]
Hypophysitis KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 0 0 0 [0;0] 0 [0;0]
Hypophysitis _ALL Pembrolizumab 10 mg/kg Q3W
84 672 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Hypophysitis KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 2 1 3 [0;7] 1 [0;4]
Hypophysitis _ALL Pembrolizumab 2 mg/kg Q3W
89 712 2 1 3 [0;7] 1 [0;4]
Hypopituitarism CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 3 2 1 [0;2] 1 [0;1]
Hypopituitarism _ALL Ipilimumab 3 mg/kg Q3W 131 3642 3 2 1 [0;2] 1 [0;1]
Hypotension CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 1 0 0 [0;1] 0 [0;0]
Hypotension _ALL Nivolumab 3mg/kg Q2W 206 3440 1 0 0 [0;1] 0 [0;0]
Hypothyroidism CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 47 1 12 [9;16] 0 [0;1]
Hypothyroidism CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 15 0 15 [7;22] 0 [0;0]
Hypothyroidism _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 62 1 13 [10;16] 0 [0;1]
Hypothyroidism CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 2 0 1 [0;1] 0 [0;0]
Hypothyroidism CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 13 0 3 [2;5] 0 [0;0]
Hypothyroidism CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 7 0 14 [4;24] 0 [0;0]
Hypothyroidism KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 2 0 1 [0;2] 0 [0;0]
Hypothyroidism _ALL Ipilimumab 3 mg/kg Q3W 744 9964 24 0 2 [1;3] 0 [0;0]
Hypothyroidism CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 15 0 7 [3;10] 0 [0;0]
Hypothyroidism CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 9 0 3 [1;4] 0 [0;0]
Hypothyroidism CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 27 0 7 [4;10] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Hypothyroidism _ALL Nivolumab 3mg/kg Q2W 787 9604 51 0 5 [4;7] 0 [0;0]
Hypothyroidism KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 9 1 14 [5;24] 2 [0;5]
Hypothyroidism KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 25 1 11 [7;16] 0 [0;1]
Hypothyroidism _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 34 2 12 [8;16] 1 [0;2]
Hypothyroidism KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
Hypothyroidism KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Hypothyroidism KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 13 0 7 [3;11] 0 [0;0]
Hypothyroidism _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 16 0 5 [3;8] 0 [0;0]
Hypothyroidism KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
Hypothyroidism KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 5 0 7 [1;13] 0 [0;0]
Hypothyroidism KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 9 0 5 [2;8] 0 [0;0]
Hypothyroidism _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 15 0 5 [3;8] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Increased lipase CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 12 8 12 [5;18] 8 [2;13]
Increased lipase _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 12 8 12 [5;18] 8 [2;13]
Increased lipase CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 2 1 4 [0;9] 2 [0;6]
Increased lipase _ALL Ipilimumab 3 mg/kg Q3W 46 506 2 1 4 [0;9] 2 [0;6]
Influenza-like illness KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 4 1 2 [0;4] 0 [0;1]
Influenza-like illness _ALL Ipilimumab 3 mg/kg Q3W 256 2022 4 1 2 [0;4] 0 [0;1]
Influenza-like illness KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 3 0 5 [0;10] 0 [0;0]
Influenza-like illness KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 2 0 1 [0;2] 0 [0;0]
Influenza-like illness _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 5 0 2 [0;3] 0 [0;0]
Influenza-like illness KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Influenza-like illness KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 1 0 1 [0;4] 0 [0;0]
Influenza-like illness _ALL Pembrolizumab 10 mg/kg Q3W
224 1960 2 0 1 [0;2] 0 [0;0]
Influenza-like illness KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Influenza-like illness KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 1 0 1 [0;4] 0 [0;0]
Influenza-like illness _ALL Pembrolizumab 2 mg/kg Q3W
200 1666 2 0 1 [0;3] 0 [0;0]
Infusion Related reaction CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 3 1 1 [0;3] 0 [0;1]
Infusion Related reaction CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 9 0 3 [1;4] 0 [0;0]
Infusion Related reaction _ALL Nivolumab 3mg/kg Q2W 474 5691 12 1 2 [1;3] 0 [0;1]
Insomnia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Insomnia _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
Insomnia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 6 0 3 [1;5] 0 [0;0]
Insomnia _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 6 0 3 [1;5] 0 [0;0]
Interstitial lung disease CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 1 0 1 [0;3] 0 [0;0]
Interstitial lung disease _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 1 0 1 [0;3] 0 [0;0]
Interstitial lung disease CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 0 0 0 [0;0] 0 [0;0]
Interstitial lung disease _ALL Ipilimumab 3 mg/kg Q3W 46 506 0 0 0 [0;0] 0 [0;0]
Joint swelling KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Joint swelling _ALL Pembrolizumab 10 mg/kg Q3W
84 672 2 0 3 [0;7] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Joint swelling KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 0 0 0 [0;0] 0 [0;0]
Joint swelling _ALL Pembrolizumab 2 mg/kg Q3W
89 712 0 0 0 [0;0] 0 [0;0]
Lethargy KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 3 0 1 [0;3] 0 [0;0]
Lethargy _ALL Ipilimumab 3 mg/kg Q3W 256 2022 3 0 1 [0;3] 0 [0;0]
Lethargy KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 2 0 1 [0;2] 0 [0;0]
Lethargy _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 2 0 1 [0;2] 0 [0;0]
Lethargy KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 0 0 0 [0;0] 0 [0;0]
Lethargy _ALL Pembrolizumab 10 mg/kg Q3W
84 672 0 0 0 [0;0] 0 [0;0]
Lethargy KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 4 0 6 [0;11] 0 [0;0]
Lethargy _ALL Pembrolizumab 2 mg/kg Q3W
89 712 4 0 6 [0;11] 0 [0;0]
Lymphopenia CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 5 0 1 [0;3] 0 [0;0]
Lymphopenia _ALL Nivolumab 3mg/kg Q2W 206 3440 5 0 1 [0;3] 0 [0;0]
Malaise CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 1 0 0 [0;1] 0 [0;0]
Malaise _ALL Nivolumab 3mg/kg Q2W 206 3440 1 0 0 [0;1] 0 [0;0]
Memory impairment KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Memory impairment _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
Memory impairment KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
Memory impairment _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 3 0 1 [0;3] 0 [0;0]
Mucosal inflammation KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 3 0 1 [0;3] 0 [0;0]
Mucosal inflammation _ALL Ipilimumab 3 mg/kg Q3W 256 2022 3 0 1 [0;3] 0 [0;0]
Mucosal inflammation KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 1 0 0 [0;1] 0 [0;0]
Mucosal inflammation _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 1 0 0 [0;1] 0 [0;0]
Mucosal inflammation KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 1 0 1 [0;4] 0 [0;0]
Mucosal inflammation _ALL Pembrolizumab 10 mg/kg Q3W
84 672 1 0 1 [0;4] 0 [0;0]
Mucosal inflammation KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 1 0 1 [0;4] 0 [0;0]
Mucosal inflammation _ALL Pembrolizumab 2 mg/kg Q3W
89 712 1 0 1 [0;4] 0 [0;0]
Muscle spasms KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Muscle spasms _ALL Ipilimumab 3 mg/kg Q3W 256 2022 1 0 0 [0;1] 0 [0;0]
Muscle spasms KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Muscle spasms KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 4 0 2 [0;4] 0 [0;0]
Muscle spasms _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 4 0 1 [0;3] 0 [0;0]
Muscle spasms KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
Muscle spasms KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Muscle spasms _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 3 0 2 [0;5] 0 [0;0]
Muscle spasms KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
Muscle spasms KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 2 0 3 [0;7] 0 [0;0]
Muscle spasms _ALL Pembrolizumab 2 mg/kg Q3W
111 954 3 0 3 [0;7] 0 [0;0]
Muscular weakness KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 1 0 2 [0;5] 0 [0;0]
Muscular weakness _ALL Pembrolizumab Pembrolizumab 10 mg/kg Q2W
57 627 1 0 2 [0;5] 0 [0;0]
Muscular weakness KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Muscular weakness KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 3 0 4 [0;10] 0 [0;0]
Muscular weakness _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 4 0 3 [0;6] 0 [0;0]
Muscular weakness KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Muscular weakness KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 3 1 4 [0;9] 1 [0;4]
Muscular weakness _ALL Pembrolizumab 2 mg/kg Q3W
111 954 3 1 3 [0;7] 1 [0;3]
Muskuloskeletal stiffness KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Muskuloskeletal stiffness _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
Muskuloskeletal stiffness KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
Muskuloskeletal stiffness _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 3 0 1 [0;3] 0 [0;0]
Myalgia CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 9 0 9 [3;14] 0 [0;0]
Myalgia _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 9 0 9 [3;14] 0 [0;0]
Myalgia CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 6 0 12 [2;21] 0 [0;0]
Myalgia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 5 1 2 [0;5] 0 [0;1]
Myalgia _ALL Ipilimumab 3 mg/kg Q3W 302 2528 11 1 4 [2;7] 0 [0;1]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Myalgia CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 9 0 3 [1;4] 0 [0;0]
Myalgia _ALL Nivolumab 3mg/kg Q2W 206 3440 9 0 3 [1;4] 0 [0;0]
Myalgia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 19 1 9 [5;13] 0 [0;1]
Myalgia _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 19 1 9 [5;13] 0 [0;1]
Myalgia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 4 0 6 [0;12] 0 [0;0]
Myalgia KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 7 0 4 [1;7] 0 [0;0]
Myalgia _ALL Pembrolizumab 10 mg/kg Q3W
263 2462 11 0 4 [2;7] 0 [0;0]
Myalgia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 5 0 7 [1;13] 0 [0;0]
Myalgia KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 9 2 5 [2;8] 1 [0;3]
Myalgia _ALL Pembrolizumab 2 mg/kg Q3W
267 2492 14 2 6 [3;9] 1 [0;2]
Nasal congestion KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 0 0 0 [0;0] 0 [0;0]
Nasal congestion _ALL Pembrolizumab 10 mg/kg Q2W
57 627 0 0 0 [0;0] 0 [0;0]
Nasal congestion KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 2 0 3 [0;8] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Nasal congestion _ALL Pembrolizumab 10 mg/kg Q3W
56 616 2 0 3 [0;8] 0 [0;0]
Nasal congestion KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Nasal congestion _ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Nausea CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 81 7 21 [17;26] 2 [0;3]
Nausea CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 21 1 20 [12;29] 1 [0;3]
Nausea _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 102 8 21 [17;25] 2 [1;3]
Nausea CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 46 3 13 [9;16] 1 [0;2]
Nausea CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 50 2 13 [10;17] 1 [0;1]
Nausea CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 11 1 22 [9;35] 2 [0;6]
Nausea KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 22 1 11 [6;15] 0 [0;1]
Nausea _ALL Ipilimumab 3 mg/kg Q3W 744 9964 129 7 13 [11;15] 1 [0;1]
Nausea CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 25 0 11 [7;15] 0 [0;0]
Nausea CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 34 0 10 [7;13] 0 [0;0]
Nausea CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 41 0 10 [7;14] 0 [0;0]
Nausea _ALL Nivolumab 3mg/kg Q2W 787 9604 100 0 10 [8;12] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Nausea KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 7 0 11 [3;19] 0 [0;0]
Nausea KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 28 0 13 [8;17] 0 [0;0]
Nausea _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 35 0 12 [8;17] 0 [0;0]
Nausea KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 4 0 6 [0;13] 0 [0;0]
Nausea KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 11 0 16 [7;26] 0 [0;0]
Nausea KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 15 1 8 [4;13] 1 [0;2]
Nausea _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 30 1 10 [6;13] 0 [0;1]
Nausea KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 2 0 8 [0;20] 0 [0;0]
Nausea KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 7 0 10 [3;17] 0 [0;0]
Nausea KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 8 0 4 [1;8] 0 [0;0]
Nausea _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 17 0 6 [3;9] 0 [0;0]
Neck pain KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 1 0 2 [0;5] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Neck pain _ALL Pembrolizumab 10 mg/kg Q2W
57 627 1 0 2 [0;5] 0 [0;0]
Neck pain KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
Neck pain _ALL Pembrolizumab 10 mg/kg Q3W
56 616 1 0 2 [0;5] 0 [0;0]
Neck pain KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Neck pain _ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Neutropenia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Neutropenia _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
Neutropenia CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 0 0 0 [0;0] 0 [0;0]
Neutropenia CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 0 0 0 [0;0] 0 [0;0]
Neutropenia _ALL Nivolumab 3mg/kg Q2W 474 5691 0 0 0 [0;0] 0 [0;0]
Neutropenia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
Neutropenia _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 3 0 1 [0;3] 0 [0;0]
Neutropenia KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 1 0 1 [0;2] 0 [0;0]
Neutropenia _ALL Pembrolizumab 10 mg/kg Q3W
179 1790 1 0 1 [0;2] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Neutropenia KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 1 0 1 [0;2] 0 [0;0]
Neutropenia _ALL Pembrolizumab 2 mg/kg Q3W
178 1780 1 0 1 [0;2] 0 [0;0]
Night sweats KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 3 0 5 [0;10] 0 [0;0]
Night sweats _ALL Pembrolizumab 10 mg/kg Q2W
57 627 3 0 5 [0;10] 0 [0;0]
Night sweats KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Night sweats KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 1 0 1 [0;4] 0 [0;0]
Night sweats _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 1 0 1 [0;2] 0 [0;0]
Night sweats KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Night sweats KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 4 0 6 [0;11] 0 [0;0]
Night sweats _ALL Pembrolizumab 2 mg/kg Q3W
111 954 4 0 4 [0;8] 0 [0;0]
Oropharyngeal pain KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Oropharyngeal pain _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
Oropharyngeal pain KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Oropharyngeal pain _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 3 0 1 [0;3] 0 [0;0]
Pain KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 0 0 0 [0;0] 0 [0;0]
Pain _ALL Pembrolizumab 10 mg/kg Q3W
84 672 0 0 0 [0;0] 0 [0;0]
Pain KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 2 0 3 [0;7] 0 [0;0]
Pain _ALL Pembrolizumab 2 mg/kg Q3W
89 712 2 0 3 [0;7] 0 [0;0]
Pain in extermity KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Pain in extermity _ALL Ipilimumab 3 mg/kg Q3W 256 2022 1 0 0 [0;1] 0 [0;0]
Pain in extermity CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 6 0 2 [0;3] 0 [0;0]
Pain in extermity _ALL Nivolumab 3mg/kg Q2W 206 3440 6 0 2 [0;3] 0 [0;0]
Pain in extermity KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 1 0 2 [0;5] 0 [0;0]
Pain in extermity KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 6 1 3 [1;5] 0 [0;1]
Pain in extermity _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 7 1 2 [1;4] 0 [0;1]
Pain in extermity KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Pain in extermity _ALL Pembrolizumab 10 mg/kg Q3W
56 616 1 0 2 [0;5] 0 [0;0]
Pain in extermity KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
Pain in extermity _ALL Pembrolizumab 2 mg/kg Q3W
22 242 1 0 4 [0;12] 0 [0;0]
Pain in jaw KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 1 0 1 [0;4] 0 [0;0]
Pain in jaw _ALL Pembrolizumab 10 mg/kg Q3W
84 672 1 0 1 [0;4] 0 [0;0]
Pain in jaw KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 1 0 1 [0;4] 0 [0;0]
Pain in jaw _ALL Pembrolizumab 2 mg/kg Q3W
89 712 1 0 1 [0;4] 0 [0;0]
Palpitations CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 1 0 0 [0;1] 0 [0;0]
Palpitations _ALL Nivolumab 3mg/kg Q2W 206 3440 1 0 0 [0;1] 0 [0;0]
Papule KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Papule _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
Papule KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
Papule _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 3 0 1 [0;3] 0 [0;0]
Paresthesia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 3 1 1 [0;3] 0 [0;1]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Paresthesia _ALL Ipilimumab 3 mg/kg Q3W 256 2022 3 1 1 [0;3] 0 [0;1]
Paresthesia CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 2 0 1 [0;1] 0 [0;0]
Paresthesia _ALL Nivolumab 3mg/kg Q2W 206 3440 2 0 1 [0;1] 0 [0;0]
Paresthesia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 0 0 0 [0;0] 0 [0;0]
Paresthesia _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 0 0 0 [0;0] 0 [0;0]
Paresthesia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Paresthesia KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 2 0 1 [0;3] 0 [0;0]
Paresthesia _ALL Pembrolizumab 10 mg/kg Q3W
263 2462 4 0 2 [0;3] 0 [0;0]
Paresthesia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 0 0 0 [0;0] 0 [0;0]
Paresthesia KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 1 0 1 [0;2] 0 [0;0]
Paresthesia _ALL Pembrolizumab 2 mg/kg Q3W
267 2492 1 0 0 [0;1] 0 [0;0]
Peripheral edema KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Peripheral edema _ALL Ipilimumab 3 mg/kg Q3W 256 2022 1 0 0 [0;1] 0 [0;0]
Peripheral edema KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Peripheral edema _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 3 0 1 [0;3] 0 [0;0]
Peripheral neuropathy KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 3 0 5 [0;10] 0 [0;0]
Peripheral neuropathy _ALL Pembrolizumab 10 mg/kg Q2W
57 627 3 0 5 [0;10] 0 [0;0]
Peripheral neuropathy KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Peripheral neuropathy KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Peripheral neuropathy KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 0 0 0 [0;0] 0 [0;0]
Peripheral neuropathy _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 2 0 1 [0;2] 0 [0;0]
Peripheral neuropathy KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Peripheral neuropathy KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 1 0 1 [0;4] 0 [0;0]
Peripheral neuropathy KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 2 0 1 [0;3] 0 [0;0]
Peripheral neuropathy _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 3 0 1 [0;2] 0 [0;0]
Peripheral oedema KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 3 0 5 [0;10] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Peripheral oedema _ALL Pembrolizumab 10 mg/kg Q2W
57 627 3 0 5 [0;10] 0 [0;0]
Peripheral oedema KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
Peripheral oedema KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 3 0 4 [0;10] 0 [0;0]
Peripheral oedema _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 4 0 3 [0;6] 0 [0;0]
Peripheral oedema KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Peripheral oedema KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 4 0 6 [0;11] 0 [0;0]
Peripheral oedema _ALL Pembrolizumab 2 mg/kg Q3W
111 954 4 0 4 [0;8] 0 [0;0]
Photosensitivity reaction CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 3 0 1 [0;2] 0 [0;0]
Photosensitivity reaction _ALL Nivolumab 3mg/kg Q2W 206 3440 3 0 1 [0;2] 0 [0;0]
Pigmentation disorder KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 0 0 0 [0;0] 0 [0;0]
Pigmentation disorder _ALL Pembrolizumab 10 mg/kg Q3W
84 672 0 0 0 [0;0] 0 [0;0]
Pigmentation disorder KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 2 0 3 [0;7] 0 [0;0]
Pigmentation disorder _ALL Pembrolizumab 2 mg/kg Q3W
89 712 2 0 3 [0;7] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Pneumonitis CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 20 3 5 [3;8] 1 [0;2]
Pneumonitis CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 10 2 10 [4;16] 2 [0;5]
Pneumonitis _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 30 5 6 [4;8] 1 [0;2]
Pneumonitis CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 5 1 1 [0;2] 0 [0;1]
Pneumonitis CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 2 1 4 [0;9] 2 [0;6]
Pneumonitis _ALL Ipilimumab 3 mg/kg Q3W 357 4300 7 2 2 [0;3] 0 [0;1]
Pneumonitis CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 5 0 2 [0;4] 0 [0;0]
Pneumonitis CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 3 0 1 [0;2] 0 [0;0]
Pneumonitis CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 4 1 1 [0;2] 0 [0;1]
Pneumonitis _ALL Nivolumab 3mg/kg Q2W 787 9604 12 1 1 [1;2] 0 [0;0]
Pneumonitis KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 4 0 6 [0;13] 0 [0;0]
Pneumonitis _ALL Pembrolizumab 10 mg/kg Q2W
57 627 4 0 6 [0;13] 0 [0;0]
Pneumonitis KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 2 0 3 [0;8] 0 [0;0]
Pneumonitis KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 1 0 1 [0;4] 0 [0;0]
Pneumonitis _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 3 0 2 [0;5] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Pneumonitis KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Pneumonitis KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 2 1 3 [0;7] 1 [0;4]
Pneumonitis _ALL Pembrolizumab 2 mg/kg Q3W
111 954 2 1 2 [0;5] 1 [0;3]
Productive cough KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 2 0 3 [0;8] 0 [0;0]
Productive cough _ALL Pembrolizumab 10 mg/kg Q2W
57 627 2 0 3 [0;8] 0 [0;0]
Productive cough KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Productive cough _ALL Pembrolizumab 10 mg/kg Q3W
56 616 0 0 0 [0;0] 0 [0;0]
Productive cough KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Productive cough _ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Pruritus CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 104 6 27 [22;32] 2 [0;3]
Pruritus CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 33 1 32 [21;43] 1 [0;3]
Pruritus _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 137 7 28 [24;33] 1 [0;3]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Pruritus CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 32 0 9 [6;12] 0 [0;0]
Pruritus CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 110 1 29 [24;34] 0 [0;1]
Pruritus CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 13 0 26 [12;40] 0 [0;0]
Pruritus KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 65 1 32 [24;40] 0 [0;1]
Pruritus _ALL Ipilimumab 3 mg/kg Q3W 744 9964 220 2 22 [19;25] 0 [0;0]
Pruritus CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 43 0 19 [13;25] 0 [0;0]
Pruritus CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 35 1 10 [7;14] 0 [0;1]
Pruritus _ALL Nivolumab 3mg/kg Q2W 474 5691 78 1 14 [11;17] 0 [0;1]
Pruritus KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 15 0 24 [12;36] 0 [0;0]
Pruritus KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 40 0 18 [13;24] 0 [0;0]
Pruritus _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 55 0 19 [14;25] 0 [0;0]
Pruritus KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 9 0 15 [5;24] 0 [0;0]
Pruritus KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 16 0 24 [12;35] 0 [0;0]
Pruritus KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 42 0 23 [16;31] 0 [0;0]
Pruritus _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 67 0 22 [17;27] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Pruritus KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 4 1 17 [0;33] 4 [0;12]
Pruritus KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 23 0 32 [19;46] 0 [0;0]
Pruritus KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 37 0 21 [14;27] 0 [0;0]
Pruritus _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 64 1 23 [18;29] 0 [0;1]
Pyrexia CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 58 2 15 [11;19] 1 [0;1]
Pyrexia CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 19 3 18 [10;27] 3 [0;6]
Pyrexia _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 77 5 16 [12;19] 1 [0;2]
Pyrexia CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 16 0 4 [2;7] 0 [0;0]
Pyrexia CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 21 1 6 [3;8] 0 [0;1]
Pyrexia CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 7 0 14 [4;24] 0 [0;0]
Pyrexia KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 6 0 3 [1;5] 0 [0;0]
Pyrexia _ALL Ipilimumab 3 mg/kg Q3W 744 9964 50 1 5 [4;6] 0 [0;0]
Pyrexia CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 15 0 4 [2;7] 0 [0;0]
Pyrexia CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 18 0 5 [2;7] 0 [0;0]
Pyrexia _ALL Nivolumab 3mg/kg Q2W 519 7353 33 0 4 [3;6] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Pyrexia KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 7 0 11 [3;19] 0 [0;0]
Pyrexia KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 11 0 5 [2;8] 0 [0;0]
Pyrexia _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 18 0 6 [3;9] 0 [0;0]
Pyrexia KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 3 0 5 [0;10] 0 [0;0]
Pyrexia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 5 0 7 [1;14] 0 [0;0]
Pyrexia _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 8 0 6 [2;11] 0 [0;0]
Pyrexia KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Pyrexia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 3 0 4 [0;9] 0 [0;0]
Pyrexia _ALL Pembrolizumab 2 mg/kg Q3W
111 954 3 0 3 [0;7] 0 [0;0]
Rash CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 89 9 23 [18;28] 2 [1;4]
Rash CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 39 5 38 [26;50] 5 [1;9]
Rash _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 128 14 26 [22;31] 3 [1;4]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Rash CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 25 1 7 [4;10] 0 [0;1]
Rash CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 102 6 27 [22;32] 2 [0;3]
Rash CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 12 0 24 [10;37] 0 [0;0]
Rash KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 37 2 18 [12;24] 1 [0;2]
Rash _ALL Ipilimumab 3 mg/kg Q3W 744 9964 176 9 18 [15;20] 1 [0;1]
Rash CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 25 1 11 [7;15] 0 [0;1]
Rash CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 31 1 9 [6;12] 0 [0;1]
Rash CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 81 2 21 [16;25] 1 [0;1]
Rash _ALL Nivolumab 3mg/kg Q2W 787 9604 137 4 14 [12;17] 0 [0;1]
Rash KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 15 2 24 [12;36] 3 [0;8]
Rash KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 41 0 19 [13;24] 0 [0;0]
Rash _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 56 2 20 [15;25] 1 [0;2]
Rash KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 10 0 16 [6;26] 0 [0;0]
Rash KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 15 1 22 [11;34] 1 [0;4]
Rash KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 18 0 10 [5;15] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Rash _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 43 1 14 [10;18] 0 [0;1]
Rash KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 3 1 12 [0;26] 4 [0;12]
Rash KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 16 0 22 [11;33] 0 [0;0]
Rash KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 21 0 12 [7;17] 0 [0;0]
Rash _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 40 1 15 [10;19] 0 [0;1]
Rash erythematous KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 1 0 0 [0;1] 0 [0;0]
Rash erythematous _ALL Ipilimumab 3 mg/kg Q3W 256 2022 1 0 0 [0;1] 0 [0;0]
Rash erythematous CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 3 0 1 [0;3] 0 [0;0]
Rash erythematous _ALL Nivolumab 3mg/kg Q2W 268 2251 3 0 1 [0;3] 0 [0;0]
Rash erythematous KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
Rash erythematous _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 3 0 1 [0;3] 0 [0;0]
Rash generalised KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Rash generalised _ALL Pembrolizumab 10 mg/kg Q3W
84 672 2 0 3 [0;7] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Rash generalised KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 1 0 1 [0;4] 0 [0;0]
Rash generalised _ALL Pembrolizumab 2 mg/kg Q3W
89 712 1 0 1 [0;4] 0 [0;0]
Rash maculopapular CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 37 6 10 [7;13] 2 [0;3]
Rash maculopapular CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 15 3 15 [7;22] 3 [0;6]
Rash maculopapular _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 52 9 11 [8;14] 2 [1;3]
Rash maculopapular CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 37 1 10 [7;13] 0 [0;1]
Rash maculopapular CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 8 0 16 [5;27] 0 [0;0]
Rash maculopapular KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 7 1 3 [1;6] 0 [0;1]
Rash maculopapular _ALL Ipilimumab 3 mg/kg Q3W 613 6323 52 2 8 [6;10] 0 [0;1]
Rash maculopapular CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 14 0 6 [3;9] 0 [0;0]
Rash maculopapular CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 6 1 2 [0;3] 0 [0;1]
Rash maculopapular _ALL Nivolumab 3mg/kg Q2W 474 5691 20 1 4 [2;5] 0 [0;1]
Rash maculopapular KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 1 0 2 [0;5] 0 [0;0]
Rash maculopapular KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 10 0 5 [2;7] 0 [0;0]
Rash maculopapular _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 11 0 4 [2;6] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Rash maculopapular KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
Rash maculopapular KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 1 3 [0;7] 1 [0;4]
Rash maculopapular KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 10 1 6 [2;9] 1 [0;2]
Rash maculopapular _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 13 2 4 [2;7] 1 [0;2]
Rash maculopapular KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Rash maculopapular KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 2 0 3 [0;7] 0 [0;0]
Rash maculopapular KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 5 1 3 [0;5] 1 [0;2]
Rash maculopapular _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 7 1 3 [1;4] 0 [0;1]
Rash papular KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 3 0 1 [0;3] 0 [0;0]
Rash papular _ALL Ipilimumab 3 mg/kg Q3W 256 2022 3 0 1 [0;3] 0 [0;0]
Rash papular CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 5 0 1 [0;3] 0 [0;0]
Rash papular _ALL Nivolumab 3mg/kg Q2W 206 3440 5 0 1 [0;3] 0 [0;0]
Rash papular KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Rash papular _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 0 0 0 [0;0] 0 [0;0]
Rash pruritic CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 3 0 3 [0;6] 0 [0;0]
Rash pruritic _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 3 0 3 [0;6] 0 [0;0]
Rash pruritic CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 5 0 10 [1;19] 0 [0;0]
Rash pruritic KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 4 0 2 [0;4] 0 [0;0]
Rash pruritic _ALL Ipilimumab 3 mg/kg Q3W 302 2528 9 0 4 [1;6] 0 [0;0]
Rash pruritic KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 4 0 2 [0;4] 0 [0;0]
Rash pruritic _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 4 0 2 [0;4] 0 [0;0]
Renal failure CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 1 0 1 [0;3] 0 [0;0]
Renal failure _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 1 0 1 [0;3] 0 [0;0]
Renal failure CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 0 0 0 [0;0] 0 [0;0]
Renal failure _ALL Ipilimumab 3 mg/kg Q3W 46 506 0 0 0 [0;0] 0 [0;0]
Renal failure CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 2 0 1 [0;1] 0 [0;0]
Renal failure _ALL Nivolumab 3mg/kg Q2W 206 3440 2 0 1 [0;1] 0 [0;0]
Renal failure KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 2 2 3 [0;8] 3 [0;8]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Renal failure _ALL Pembrolizumab 10 mg/kg Q2W
57 627 2 2 3 [0;8] 3 [0;8]
Renal failure KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
Renal failure _ALL Pembrolizumab 10 mg/kg Q3W
56 616 1 0 2 [0;5] 0 [0;0]
Renal failure KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Renal failure _ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
Skin hypopigmentation KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Skin hypopigmentation _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
Skin hypopigmentation KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 5 0 2 [0;4] 0 [0;0]
Skin hypopigmentation _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 5 0 2 [0;4] 0 [0;0]
Skin hypopigmentation KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Skin hypopigmentation _ALL Pembrolizumab 10 mg/kg Q3W
84 672 2 0 3 [0;7] 0 [0;0]
Skin hypopigmentation KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 0 0 0 [0;0] 0 [0;0]
Skin hypopigmentation _ALL Pembrolizumab 2 mg/kg Q3W
89 712 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Skin lesion KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Skin lesion _ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
Skin lesion KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 1 0 0 [0;1] 0 [0;0]
Skin lesion _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 1 0 0 [0;1] 0 [0;0]
Soft feces KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 3 0 1 [0;3] 0 [0;0]
Soft feces _ALL Ipilimumab 3 mg/kg Q3W 256 2022 3 0 1 [0;3] 0 [0;0]
Soft feces KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 1 0 0 [0;1] 0 [0;0]
Soft feces _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 1 0 0 [0;1] 0 [0;0]
Thrombocytopenia CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 0 0 0 [0;0] 0 [0;0]
Thrombocytopenia _ALL Nivolumab 3mg/kg Q2W 206 3440 0 0 0 [0;0] 0 [0;0]
Thrombocytopenia KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 1 0 2 [0;5] 0 [0;0]
Thrombocytopenia _ALL Pembrolizumab 10 mg/kg Q2W
57 627 1 0 2 [0;5] 0 [0;0]
Thrombocytopenia KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
Thrombocytopenia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Thrombocytopenia KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 2 1 1 [0;3] 1 [0;2]
Thrombocytopenia _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 5 1 2 [0;3] 0 [0;1]
Thrombocytopenia KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 2 0 8 [0;20] 0 [0;0]
Thrombocytopenia KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 0 0 0 [0;0] 0 [0;0]
Thrombocytopenia KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 2 0 1 [0;3] 0 [0;0]
Thrombocytopenia _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 4 0 1 [0;3] 0 [0;0]
Thyroxine decreased KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 3 0 4 [0;10] 0 [0;0]
Thyroxine decreased _ALL Pembrolizumab 10 mg/kg Q3W
84 672 3 0 4 [0;10] 0 [0;0]
Thyroxine decreased KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 1 0 1 [0;4] 0 [0;0]
Thyroxine decreased _ALL Pembrolizumab 2 mg/kg Q3W
89 712 1 0 1 [0;4] 0 [0;0]
Tumour pain KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Tumour pain _ALL Pembrolizumab 10 mg/kg Q3W
84 672 2 0 3 [0;7] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Tumour pain KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 1 0 1 [0;4] 0 [0;0]
Tumour pain _ALL Pembrolizumab 2 mg/kg Q3W
89 712 1 0 1 [0;4] 0 [0;0]
Upper respiratory tract infection
KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 0 0 0 [0;0] 0 [0;0]
Upper respiratory tract infection
_ALL Ipilimumab 3 mg/kg Q3W 256 2022 0 0 0 [0;0] 0 [0;0]
Upper respiratory tract infection
KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
Upper respiratory tract infection
_ALL Pembrolizumab 10 mg/kg Q2W
278 2196 3 0 1 [0;3] 0 [0;0]
Uveitis KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 0 0 0 [0;0] 0 [0;0]
Uveitis _ALL Pembrolizumab 10 mg/kg Q2W
57 627 0 0 0 [0;0] 0 [0;0]
Uveitis KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 2 0 3 [0;8] 0 [0;0]
Uveitis _ALL Pembrolizumab 10 mg/kg Q3W
56 616 2 0 3 [0;8] 0 [0;0]
Uveitis KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Uveitis _ALL Pembrolizumab 2 mg/kg Q3W
22 242 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Vertigo CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 2 0 1 [0;1] 0 [0;0]
Vertigo _ALL Nivolumab 3mg/kg Q2W 206 3440 2 0 1 [0;1] 0 [0;0]
Vertigo KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Vertigo _ALL Pembrolizumab 10 mg/kg Q3W
84 672 2 0 3 [0;7] 0 [0;0]
Vertigo KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 0 0 0 [0;0] 0 [0;0]
Vertigo _ALL Pembrolizumab 2 mg/kg Q3W
89 712 0 0 0 [0;0] 0 [0;0]
Vision blurred KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 3 0 1 [0;3] 0 [0;0]
Vision blurred _ALL Ipilimumab 3 mg/kg Q3W 256 2022 3 0 1 [0;3] 0 [0;0]
Vision blurred KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 1 0 0 [0;1] 0 [0;0]
Vision blurred _ALL Pembrolizumab 10 mg/kg Q2W
278 2196 1 0 0 [0;1] 0 [0;0]
Visual impairment KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 1 0 2 [0;5] 0 [0;0]
Visual impairment _ALL Pembrolizumab 10 mg/kg Q2W
57 627 1 0 2 [0;5] 0 [0;0]
Visual impairment KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Visual impairment KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 0 0 0 [0;0] 0 [0;0]
Visual impairment _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 0 0 0 [0;0] 0 [0;0]
Visual impairment KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
Visual impairment KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 2 0 3 [0;7] 0 [0;0]
Visual impairment _ALL Pembrolizumab 2 mg/kg Q3W
111 954 3 0 3 [0;7] 0 [0;0]
Vitiligo CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 21 0 5 [3;8] 0 [0;0]
Vitiligo CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 10 0 10 [4;16] 0 [0;0]
Vitiligo _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 31 0 6 [4;9] 0 [0;0]
Vitiligo CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 3 0 1 [0;2] 0 [0;0]
Vitiligo CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 12 0 3 [1;5] 0 [0;0]
Vitiligo CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 4 0 8 [0;16] 0 [0;0]
Vitiligo KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 4 0 2 [0;4] 0 [0;0]
Vitiligo _ALL Ipilimumab 3 mg/kg Q3W 744 9964 23 0 2 [1;3] 0 [0;0]
Vitiligo CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 14 0 6 [3;9] 0 [0;0]
Vitiligo CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 22 0 6 [4;9] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Vitiligo _ALL Nivolumab 3mg/kg Q2W 474 5691 36 0 6 [4;8] 0 [0;0]
Vitiligo KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 7 0 11 [3;19] 0 [0;0]
Vitiligo KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 25 0 11 [7;16] 0 [0;0]
Vitiligo _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 32 0 11 [7;15] 0 [0;0]
Vitiligo KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 4 0 6 [0;13] 0 [0;0]
Vitiligo KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 5 0 7 [1;14] 0 [0;0]
Vitiligo KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 9 0 5 [2;8] 0 [0;0]
Vitiligo _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 18 0 6 [3;9] 0 [0;0]
Vitiligo KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
Vitiligo KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 8 0 11 [3;19] 0 [0;0]
Vitiligo KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 10 0 6 [2;9] 0 [0;0]
Vitiligo _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 19 0 7 [4;10] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Vomiting CheckMate-067 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
313 minimum 3819 48 8 13 [9;16] 2 [1;4]
Vomiting CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 13 1 13 [6;19] 1 [0;3]
Vomiting _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
407 4853 61 9 13 [9;16] 2 [1;3]
Vomiting CA-184-002 Ipilimumab 3 mg/kg Q3W 131 median 3642 31 3 9 [6;12] 1 [0;2]
Vomiting CheckMate-067 Ipilimumab 3 mg/kg Q3W 311 minimum 3794 23 1 6 [4;9] 0 [0;1]
Vomiting CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 5 0 10 [1;19] 0 [0;0]
Vomiting KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 14 0 7 [3;11] 0 [0;0]
Vomiting _ALL Ipilimumab 3 mg/kg Q3W 744 9964 73 4 7 [6;9] 0 [0;1]
Vomiting CheckMate-037 Nivolumab 3mg/kg Q2W 268 median 2251 8 1 4 [1;6] 0 [0;1]
Vomiting CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 13 1 4 [2;6] 0 [0;1]
Vomiting CheckMate-067 Nivolumab 3mg/kg Q2W 313 median 3913 20 1 5 [3;7] 0 [0;1]
Vomiting _ALL Nivolumab 3mg/kg Q2W 787 9604 41 3 4 [3;6] 0 [0;1]
Vomiting KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 3 1 5 [0;10] 2 [0;5]
Vomiting KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 10 1 5 [2;7] 0 [0;1]
Vomiting _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 13 2 5 [2;7] 1 [0;2]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Vomiting KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
Vomiting KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 3 0 4 [0;10] 0 [0;0]
Vomiting KEYNOTE-002 Pembrolizumab 10 mg/kg Q3W
179 median 1790 10 1 6 [2;9] 1 [0;2]
Vomiting _ALL Pembrolizumab 10 mg/kg Q3W
319 3078 14 1 5 [2;7] 0 [0;1]
Vomiting KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Vomiting KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 2 0 3 [0;7] 0 [0;0]
Vomiting KEYNOTE-002 Pembrolizumab 2 mg/kg Q3W
178 median 1780 2 1 1 [0;3] 1 [0;2]
Vomiting _ALL Pembrolizumab 2 mg/kg Q3W
289 2734 4 1 1 [0;3] 0 [0;1]
Weight decreased KEYNOTE-006 Ipilimumab 3 mg/kg Q3W 256 median 2022 5 1 2 [0;5] 0 [0;1]
Weight decreased _ALL Ipilimumab 3 mg/kg Q3W 256 2022 5 1 2 [0;5] 0 [0;1]
Weight decreased KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 2 0 3 [0;8] 0 [0;0]
Weight decreased KEYNOTE-006 Pembrolizumab 10 mg/kg Q2W
278 median 2196 3 0 1 [0;3] 0 [0;0]
Weight decreased _ALL Pembrolizumab 10 mg/kg Q2W
335 2823 5 0 2 [0;3] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
Weight decreased KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 0 0 0 [0;0] 0 [0;0]
Weight decreased KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Weight decreased _ALL Pembrolizumab 10 mg/kg Q3W
140 1288 2 0 2 [0;4] 0 [0;0]
Weight decreased KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 0 0 0 [0;0] 0 [0;0]
Weight decreased KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 3 0 4 [0;9] 0 [0;0]
Weight decreased _ALL Pembrolizumab 2 mg/kg Q3W
111 954 3 0 3 [0;7] 0 [0;0]
Wheezing KEYNOTE-001 (randomized cohorts)
Pembrolizumab 10 mg/kg Q3W
84 median 672 2 0 3 [0;7] 0 [0;0]
Wheezing _ALL Pembrolizumab 10 mg/kg Q3W
84 672 2 0 3 [0;7] 0 [0;0]
Wheezing KEYNOTE-001 (randomized cohorts)
Pembrolizumab 2 mg/kg Q3W
89 median 712 0 0 0 [0;0] 0 [0;0]
Wheezing _ALL Pembrolizumab 2 mg/kg Q3W
89 712 0 0 0 [0;0] 0 [0;0]
leukopenia CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 1 0 0 [0;1] 0 [0;0]
leukopenia _ALL Nivolumab 3mg/kg Q2W 206 3440 1 0 0 [0;1] 0 [0;0]
leukopenia KEYNOTE-001 Pembrolizumab 10 mg/kg Q2W
57 median 627 1 0 2 [0;5] 0 [0;0]
SUPPLEMENTARY INFORMATION In format provided by Boutros et al. (SEPTEMBER 2016)
NATURE REVIEWS | CLINICAL ONCOLOGY www.nature.com/reviews/nrclinonc
Adverse event Study Regimen
N patients
Follow-up duration statistic
N patients_months
N of AEs
N of grade
3-5 AEs
AE incidence per 1000 person-
months [95%CI]
Grade 3-5 AE incidence per 1000 person-
months [95%CI]
leukopenia _ALL Pembrolizumab 10 mg/kg Q2W
57 627 1 0 2 [0;5] 0 [0;0]
leukopenia KEYNOTE-001 Pembrolizumab 10 mg/kg Q3W
56 median 616 1 0 2 [0;5] 0 [0;0]
leukopenia _ALL Pembrolizumab 10 mg/kg Q3W
56 616 1 0 2 [0;5] 0 [0;0]
leukopenia KEYNOTE-001 Pembrolizumab 2 mg/kg Q3W
22 median 242 1 0 4 [0;12] 0 [0;0]
leukopenia _ALL Pembrolizumab 2 mg/kg Q3W
22 242 1 0 4 [0;12] 0 [0;0]
renal failure acute CheckMate-069 Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 minimum 1034 0 0 0 [0;0] 0 [0;0]
renal failure acute _ALL Ipilimumab 3 mg/Kg + Nivolumab 1 mg/kg
94 1034 0 0 0 [0;0] 0 [0;0]
renal failure acute CheckMate-069 Ipilimumab 3 mg/kg Q3W 46 minimum 506 1 0 2 [0;6] 0 [0;0]
renal failure acute _ALL Ipilimumab 3 mg/kg Q3W 46 506 1 0 2 [0;6] 0 [0;0]
renal failure acute CheckMate-066 Nivolumab 3mg/kg Q2W 206 median 3440 1 1 0 [0;1] 0 [0;1]
renal failure acute _ALL Nivolumab 3mg/kg Q2W 206 3440 1 1 0 [0;1] 0 [0;1]