DIRE Cases
| 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)b22 (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]; |
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
a Cases from our institution
b Estimate from article narrative
c Tumor type was not specified, unkown age / sex