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Table 1 DIRE Cases

From: Delayed immune-related events (DIRE) after discontinuation of immunotherapy: diagnostic hazard of autoimmunity at a distance

Case Disease / age / sex Rx Setting DIRE Post IO (months) Drug Doses (total) Best Response Notes
1 HNSCC, HPV+ / 62 / M Neoadjuvant Neurosarcoidosis 28a 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 4a 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 5b 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 33b 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 36b 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];
  1. Abbreviations: IO Immuno-oncology, HNSCC Head and neck squamous cell carcinoma, NSCLC Non-small cell lung cancer, RT Radiotherapy, ICI Immune-checkpoint inhibitor, AIDP Acute inflammatory demyelinating polyneuropathy, Nivo Nivolumab, Ipi Ipilimumab, Treme Tremelimumab, NED No evidence of disease, mo Months, y Years, CR Complete response, PR partial response, SD Stable disease, PD Progressive disease
  2. a Cases from our institution
  3. b Estimate from article narrative
  4. c Tumor type was not specified, unkown age / sex