Table 3.
Main characteristics of patients with second-line immunosuppressant.
| Patient | Sex, age (years); ancer, sites of metastases | Previous ICI exposure | ICI agents | Time to CHILI onset (days) | Other irAEs | CHILI phenotype, CTCAE grade | Serum autoantibody | Serum IgG (g/L) | Histology | First-line treatment for CHILI | Second-line treatment, time from CHILI (days) | Time until resolution to grade 1 (days) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | M, 49; melanoma, lymph node | No | Combo ipilimumab + nivolumab | 20 | Vitiligo, thyroiditis | Cholestatic, grade 3 | ANA 1/320, ASMA negative | 6.84 | Interface hepatitis, eosinophilia, fibrin ring granulomas | Steroids 1.5 mg/kg, UDCA 500 mg | Mycophenolate mofetil, 92 | 136 |
| 2 | F, 54; melanoma, lymph node | No | Pembrolizumab | 220 | No | Cholestatic, grade 3 | ANA negative, ASMA negative | 4.33 | Interface hepatitis, eosinophilia, mixed cholangitis∗ | Steroids 1 mg/kg, UDCA 750 mg | Mycophenolate mofetil, 198 | 138 |
| 3 | M, 67; hypopharynx, lung | No | Nivolumab | 95 | Interstitial pneumonia | Cholestatic, grade 4 | ANA negative, ASMA negative | 6.20 | Portal fibrosis (F1) | Steroids 2 mg/kg, UDCA 500 mg | Rituximab 1 g/2 weeks, 483 | |
| 4 | F, 30; melanoma, lymph node and brain | Pembrolizumab | Combo ipilimumab + nivolumab | 62 | No | Hepatocellular, grade 3 | ANA negative, ASMA 1/160 | 9.9 | Panlobular necrotising hepatitis | Steroids 2 mg/kg | Mycophenolate mofetil, 113 | 154 |
| 5 | F, 84; melanoma, lung | Pembrolizumab, + combo ipilimumab + nivolumab | Nivolumab | 13 | No | Hepatocellular, grade 3 | ANA negative, ASMA negative | 7.7 | Lobular necrotising hepatitis, histiocytes | Steroids 2 mg/kg, UDCA 1,000 mg | Mycophenolate mofetil, 30 | 62 |
| 6 | F, 60; melanoma, lung and liver | Pembrolizumab | Combo ipilimumab + nivolumab | 11 | Colitis, dermatitis | Cholestatic, grade 3 | ANA negative, ASMA negative | n.a. | None | Steroids 1 mg/kg, UDCA 1,500 mg | Mycophenolate mofetil, 114 | 79 |
| 7 | F, 40; melanoma, lung and liver | Nivolumab | Ipilimumab | 37 | Thyroiditis | Hepatocellular, grade 4 | ANA negative, ASMA negative | n.a. | Panlobular necrotising hepatitis, histiocytes | Steroids 1 mg/kg | Mycophenolate mofetil, 30 | 180 |
| 8 | F, 79; melanoma, lymph node and lung | Combo ipilimumab + nivolumab | Nivolumab | 434 | Vitiligo, thyroiditis | Hepatocellular, grade 3 | ANA positive, ASMA 1/100 | 21 | Centrolobular fibrosis (F1) | Steroids 2 mg/kg, UDCA 1,000 mg | Mycophenolate mofetil, 18 | 69 |
| 9 | M, 54; renal cell carcinoma, lymph node and lung | No | Combo ipilimumab + nivolumab | 54 | No | Hepatocellular, grade 4 | ANA positive, ASMA 1/100 | 10 | Lobular necrotising hepatitis, histiocytes, cholangitis | Steroids 2 mg/kg, UDCA 1,000 mg | Mycophenolate mofetil, 52 | 90 |
| 10 | F, 60; melanoma, liver and spleen | No | Combo ipilimumab + nivolumab | 65 | No | Hepatocellular, grade 4 | ANA negative, ASMA negative | 12.6 | Plasmocytes, histiocytes | Steroids 4 mg/kg, UDCA 1,500 mg | Mycophenolate mofetil, 21 | 82 |
| 11 | M, 55; renal cell carcinoma, adrenal | No | Combo ipilimumab + nivolumab | 20 | No | Hepatocellular, grade 4 | ANA negative, ASMA negative | 11.3 | Panlobular necrotising hepatitis, plasmocytes, histiocytes | Steroids 1.25 mg/kg, UDCA 750 mg | Mycophenolate mofetil, 8 | 74 |
| 12 | F, 63; lung cancer, bone | No | Pembrolizumab | 33 | No | Cholestatic, grade 3 | ANA negative, ASMA negative | 14.9 | Cholangitis, plasmocytes, histiocytes | Steroids 2 mg/kg, UDCA 1,000 mg | Mycophenolate mofetil, 15 | 170 |
| 13 | F, 77; lung cancer, adrenal | No | Pembrolizumab | 93 | No | Cholestatic, grade 4 | ANA negative, ASMA negative | 4.3 | Cholangitis, ductopaenia | Steroids 2 mg/kg, UDCA 1,000 mg | Mycophenolate mofetil, 23 | 187 |
| 14 | M, 53; lung cancer, lymph node and brain | No | Combo ipilimumab + nivolumab | 62 | No | Hepatocellular, grade 4 | ANA negative, ASMA negative | 10.7 | None | Steroids 1 mg/kg | Mycophenolate mofetil, 9 | 120 |
| 15 | M, 55; renal cell carcinoma, bone | Combo ipilimumab + nivolumab | Nivolumab | 133 | Colitis | Cholestatic, grade 3 | ANA negative, ASMA negative | 8 | Cholangitis | Steroids 2 mg/kg, UDCA 1,000 mg | Mycophenolate mofetil, 147 (tacrolimus, abatacept) | 549 |
| 16 | M, 74; melanoma, lung, brain, and adrenal | No | Combo ipilimumab + nivolumab | 48 | Dermatitis, myocarditis | Hepatocellular, grade 3 | ANA negative, ASMA negative | n.a. | Centrolobular necrotising hepatitis, plasmocytes, centrolobular fibrosis (F1) | Steroids 2 mg/kg, UDCA 1,000 mg | Mycophenolate mofetil, 18 | 54 |
| 17 | M, 61, renal cell carcinoma, lung | Combo ipilimumab + nivolumab | Nivolumab | 161 | Hypophysitis, thyroiditis, myocarditis | Mixed, grade 3 | ANA negative, ASMA negative | 8 | Lobular necrotising hepatitis, cholangitis, portal fibrosis (F1) | Steroids 2 mg/kg | Mycophenolate mofetil, 27 | 162 |
| 18 | F, 49; melanoma, peritoneum | No | Combo ipilimumab + nivolumab | 42 | No | Mixed, grade 3 | ANA negative, ASMA negative | n.a. | Centrolobular hepatitis, portal fibrosis (F1) | Steroids 2 mg/kg | Mycophenolate mofetil, 7 | 15 |
ANA, N <1/160; ASMA, N <1/40.
ANA, antinuclear antibodies; ASMA, antismooth muscle antibodies; CHILI, checkpoint inhibitor-induced liver injury; CTCAE, Common Terminology Criteria for Adverse Events; ICI, immune checkpoint inhibitor; irAE, immune-related adverse event; n.a., not available.
∗
Mixed cholangitis, lymphocytic cholangitis, and non-suppurative destructive cholangitis.