Table 1 DIRE Cases

1

HNSCC, HPV+ / 62 / M

Neoadjuvant

Neurosarcoidosis

28^a

MEDI6469 (OX40 agonist)

3

N/A

Couey et al., 2019; Interim treatments: Surgical resection and adjuvant RT (2Gy × 33)

2

HNSCC, HPV+ / 62 / M

Neoadjuvant

Adrenal Insufficiency; Encephalopathy, acute

4^a

Nivolumab

2

N/A

Couey et al., 2019; Interim treatments: Surgical resection and adjuvant RT (2Gy ×  27)

3

Melanoma / 64 / F

Adjuvant

Pneumonitis

8

Nivolumab or Ipilimumab (remains blinded)

7 or 4 (blinded)

NED at 2 y

Mandalà et al., 2018 [2]; On-treatment irAE: Colitis; Interim treatments: Infliximab, Corticosteroids

4

Melanoma / 62 / F

Adjuvant

Pneumonitis

6

Nivolumab

5^b

Brain met at 4 mo

Diamantopoulos et al., 2017 [3]; On-treatment irAE: Thyroiditis, Hepatitis; Interim treatments: Methimazole

5

Melanoma / 55 / M

Adjuvant

Hypothyroidism

3

Ipilimumab

2

NED at 4 mo

Garcia et al., 2018 [4]; On-treatment irAE: AIDP, Adrenal insufficiency; Interim treatments: Corticosteroids

6

Melanoma / 63 / M

Metastatic

Colitis

23

Pembrolizumab

33^b

Not reported

Sarofim and Winn, 2018 [5]; Underwent hemicolectomy for pseudo-obstruction, final path ICI-induced colitis

7

NSCLC / 60 / M

Metastatic

Adrenal Insufficiency

15

Pembrolizumab

24

CR

Boudjemaa et al., 2018 [6];

8

Melanoma / 65 / M

Metastatic

Neurosarcoidosis

11

Ipilimumab + Nivolumab

2

SD

Tan et al., 2018 [7]; On-treatment irAE: Colitis, Transaminitis; Pulmonary sarcoidosis 1 month post-IO; interim treatments: Infliximab, Corticosteroids

9

Melanoma / 70 / M

Metastatic

Vitiligo

9

Pembrolizumab

4

PD

Hanrahan et al., 2013 [8]; Interim treatments: Corticosteroids for polymyalgia rheumatica 5 months post-IO

10

Melanoma / 77 / F

Metastatic

Hepatitis

8

Ipilimumab followed by Nivolumab

4 (Ipi)^b

22 (Nivo)^b

PR

Parakh et al., 2018 [9]; Interim treatments: RT 6Gy × 6 (adrenal met)

11

NSCLC / 73 / M

Metastatic

Adrenal Insufficiency

7

Nivolumab

4

SD

Shrotriya et al., 2018 [10]; Concurrent treatments: Gemcitabine/Vinorelbine

12

NSCLC / 66 / M

Metastatic

Adrenal Insufficiency

6

Nivolumab

11

PD

Otsubo et al., 2018 [11];

13

SCC cutaneous / 80’s / F

Metastatic

Bullous Pemphigoid

6

Pembrolizumab

4

PD

Wang et al., 2018 [12]; On-treatment irAE: Erythema multiforme

14

Melanoma / 67 / F

Metastatic

Alopecia

6

PD-1 + CTLA4

2

Not reported

Zarbo et al., 2017 [13]; On-treatment irAE: Colitis; Interim treatments: Infliximab, Corticosteroids

15

Melanoma / 65 / F

Metastatic

Pericarditis

6

Ipilimumab

4

CR

Dasanu et al., 2017 [14]; On-treatment irAE: Thyroiditis, Transaminitis, Rash; Inflamm. arthritis at 2mo & 8mo); Interim treatments: Corticosteroids

16

“Melanoma or solid tumor”^c

Metastatic

Uveitis

5

Tremelimumab + PF-3512676 (TLR9 agonist)

4 (Treme)

38 (TLR9)^b

Not reported

Millward et al., 2013 [15]; On-treatment irAE: Neutropenia (TLR9); Rectal bleeding (Treme)

17

Melanoma / 60’s / M

Metastatic

Sarcoidosis (pulmonary, cutaneous)

5

Pembrolizumab

10

CR

Wang et al., 2018 [12];

18

NSCLC / 68 / F

Recurrent

Adrenal Insufficiency

4

Nivolumab

2

PR

Otsubo et al., 2018 [11]; On-treatment irAE: Pneumonitis; Interim treatments: Corticosteroids

19

Melanoma / 63 / F

Metastatic

Myocarditis

4

Ipilimumab

8

SD

Roth et al., 2016 [16]; On-treatment irAE: Hypophysitis, Adrenal insufficiency; Interim treatments: Surgery (recurrence), Corticosteroids

20

Melanoma 65 / F

Metastatic

Alopecia

3

PD-1 + CTLA4

4

PR

Zarbo et al., 2017 [13]; On-treatment irAE: Transaminitis

21

Melanoma / 63 / F

Metastatic

Eosinophilic Fasciitis; Encephalopathy, acute

3

Pembrolizumab

36^b

CR

Khoja et al., 2016 [17]; Myalgia 1 month post-IO

22

Melanoma / 81 / F

Metastatic

Guillain–Barré Syndrome

3

Pembrolizumab

6

PD

Khoja et al., 2015 [18]; On-treatment irAE: Thyroiditis; Rash 7d after subsequent BRAF inhibitor, 1mo post-IO; Interim treatments: Corticosteroids

23

Melanoma / 59 / M

Metastatic

Adrenal Insufficiency; Pericarditis; Hypothyroidism

3

Ipilimumab

4

Not reported

Yun et al., 2015 [19];