TABLE 1.
Basic characteristics of all included studies
| Cancer | Grade of ICI hepatitis | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Study | Age | Male, n (%) | Type (n) | Stage (%) | ICI | N. received ICI | 1 | 2 | 3 | 4 | Total |
| Leroy et al8 | 82 [80–90] | 14 (60.9) | Melanoma (23) | Stage 4 | Ipilimumab | 23 | 0 | 0 | 2 | 0 | 2 |
| Luo et al9 | Lung | 51 | 6 | ||||||||
| Romanski et al10 | 60 [38–87] | 19 (44.2) | Melanoma | Stage 4 | Ipilimumab (14), pembrolizumab (16), nivolumab (1), ipilimumab + nivolumab (12) | 521 | 179 | 15 | 23 | 5 | 265 |
| Miller et al11 | 60 [IQR: 54–69] | 61 (61) | Melanoma (53), GU (14), lung, head, neck (12), GI (9), other solid (2), hematological (10) | Stage 3 (9) Stage 4 (91) |
CTLA-4 monotherapy (25), PD-1/PD-L1 monotherapy (46), combination (29) | 5762 | 0 | 0 | 85 | 15 | 100 |
| Smith et al12 | 53.8 [IQR: 46.9–60.7] | 22 (69) | Melanoma | Stage 3 (8) Stage 4 (92) |
Ipilimumab + nivolumab | 63 | 11 | 21 | 32 | ||
| Yamamoto et al13 | 70 [30–84] | 14 (66.67) | NSCLC (3), RCC (7), urothelial (1), MM (8), other (2) | Nivolumab (10), pembrolizumab (3), atezolizumab (1), ipilimumab (2), ipilimumab + nivolumab (5) | 245 | 0 | 7 | 9 | 5 | 21 | |
| Takinami et al14 | 55.5 [IQR: 54–68] | 4 (50) | Melanoma (6), renal cell (2) | Pembrolizumab (1), ipilimumab (2), ipilimumab + nivolumab (5) | 530 | 0 | 3 | 5 | 8 | ||
| Owen et al15 | Melanoma | Stage 4 | Anti-PD1, anti-PD1 + anti-CTLA4, anti-PD1 ± anti-CTLA4 | 118 | 0 | 2 | 8 | 2 | 12 | ||
| Li et al16 | 57.8 (13.7) | 47 (54.0) | Melanoma, NSCLC, RCC, breast cancer, urothelial cancer, other | Nivolumab (11), pembrolizumab (43), cemiplimab, ipilimumab (18), ipilimumab + nivolumab (49), anti–PD-L1 (7) | 7046 | 0 | 0 | 60 | 27 | 87 | |
| 61.6 (15.5) | 66 (51.6) | Nivolumab (11), pembrolizumab (14), cemiplimab (2), ipilimumab (9), ipilimumab + nivolumab (45), anti–PD-L1 (6) | 0 | 0 | 106 | 22 | 128 | ||||
| Cunningham et al17 | 47.9 (95% CI: 39.3–58.4) | 9 (52.9) | Head and neck (4), melanoma (8), pancreas (1), colorectal (2), sarcoma (1), RCC (1) | Anti-PD1 (11), anti–PD-L1 (1), anti-CTLA4 (3), combination (1), blinded (1) | 450 | 0 | 4 | 13 | 17 | ||
| Sanz-Segura et al18 | 132 | 2 | 2 | 0 | 0 | 4 | |||||
| da Silva et al19 | 65 | 2 (66.7) | Lung (2), melanoma (1) | Pembrolizumab (1), nivolumab (2) | 151 | 3 | |||||
| Huffman et al20 | 57 [32–82] | 12 (75) | Melanoma | Stage 4 | Ipilimumab (12), pembrolizumab (3), ipilimumab + nivolumab (2) | 218 | 3 | 1 | 8 | 3 | 17 |
| Cheung et al21 | 62 [21–76] | 11 (52) | Melanoma (17), renal cell (1), non–small cell lung (2), epithelial mesothelioma (1) | ipilimumab, nivolumab, pembrolizumab, ipilimumab + nivolumab, Checkmate 238 | 453 | 3 | 4 | 9 | 5 | 21 | |
| Shimomura et al22 | NSCLC | Stage 4 | Anti–PD-1 inhibitors | 375 | 18 | 10 | 6 | 0 | 34 | ||
| Swanson et al (2022) | 70 [54–86] | 1 (50) | cSCC | Cemiplimab (2) | 39 | 2 | |||||
| de la Bruyère et al24 | Melanoma (8), lung (4) | PD(L)-1 inhibitors (6), CTLA-4 inhibitors (6) | 150 | 0 | 0 | 12 | 12 | ||||
| Swanson et al (2022) | 65 [47–70] | 3 (50) | Pancreatic (3), HCC (2), RCC (1) | Stage 4 | Durvalumab combination (6) | 112 | 0 | 3 | 3 | 0 | 6 |
| Sawada et al26 | 64.0 [48–76] | 7 (87.5) | NSCLC (3), MM (1), GC (2), RCC (1), HNSCC (1) | Nivolumab (8), pembrolizumab (5), ipilimumab (4) | 135 | 0 | 3 | 5 | 0 | 8 | |
| Fan et al27 | 60 [IQR: 57–65] | 8 (38) | Bladder (2), breast (4), esophageal (2), GBM (2), gastric (2), liposarcoma (1), melanoma (3), NSCLC (3), ovarian (1), pancreatic (1) | Stage 4 (33) | CTLA-4 (20), CTLA-4 + PD-1/PD-L1 (3), PD-1/PD-L1 (16) | 331 | 6 | 15 | 21 | ||
| Kitagataya et al28 | 67 [25–92] | 9 (52.9) | Melanoma (5), lung (1), lymphoma (1), other (1) | Nivolumab (8), pembrolizumab (5), ipilimumab (4) | 202 | 3 | 6 | 6 | 2 | 17 | |
| Zheng et al29 | Anti–PD-1/PD-L1 inhibitor | 240 | 1 | 0 | 3 | 0 | 4 | ||||
| Daniello et al30 | NSCLC | Stage 4 | Anti-PD(L)1 inhibitors | 894 | 2 | 7 | 20 | 4 | 33 | ||
| Cheng et al31 | 63 [56–69] | 3 (100) | Melanoma | Stage 4 | Ipilimumab | 3 | |||||
| Pollack et al32 | Melanoma | Stage 4 | anti–PD-1 + ipilimumab | 13 | 24 | 37 | |||||
| De Martine et al33 | 63 [33–84] | 7 (44) | Melanoma (12), bronchial (1), renal clear cell (1), bladder (1), cholangiocarcinoma (1) | Stage 4 | Anti–PD-1/PD-L1 (9), anti-CTLA4 (7) | 536 | 0 | 0 | 16 | 16 | |
| Simonaggio et al34 | 159 | 0 | 4 | 8 | 5 | 17 | |||||
| Imoto et al35 | 63 [49–69] | 31 (63.6) | 387 | 45 | 11 | 56 | |||||
| Zen et al36 | 70 [59–74] | 8 (80) | NSCLC (4), urothelial (3), merkel cell (1), melanoma (1), colon (1) | Stage 4 | Pembrolizumab (6), atezolizumab (4) | 10 | |||||
| Riveiro-Barciela et al37 | 62.8 [IQR: 56.6–70.5] | 14 (50) | NSCLC (21.4%), melanoma (17.9%), urothelial (14.3%) | Anti-CTLA4 (10), anti–PD-1/PD-L1 (18) | 414 | 0 | 0 | 28 | 28 | ||
| Gauci et al38 | 52 [IQR: 47–67] | 14 (66.7) | Melanoma | Stage 3 (5), Stage 4 (95) | Ipilimumab (7), nivolumab (3), pembrolizumab (1), ipilimumab + nivolumab (10) | 339 | 0 | 0 | 10 | 11 | 21 |
| Patrinely, Jr. et al39 | 63 | 88 (53.7) | Lung (12), melanoma (138), renal (5), squamous cell (2), other (7) | Stage 4 (86) | Ipilimumab (7), ipilimumab + nivolumab (97), ipilimumab + pembrolizumab (3), nivolumab (19), pembrolizumab (34), other anti–PD-1/PD-L1 (4) | 164 | 16 | 50 | 75 | 23 | 164 |
| Rini et al40 | RCC | Stage 4 | Pembrolizumab + axitinib (429), sunitinib (425) | 861 | 125 | ||||||
| Lin et al41 | 34 (66.67) | Anti-PD1 | 1310 | 37 | 14 | 51 | |||||
| Personeni et al42 | 71 [49–83] | 5 (55.56) | HCC | BFTABLE CLC stage B or C |
Anti–PD-1/PD-L1 ± anti–CTLA–4 antibodies and/or targeted agents (including sorafenib, cabozantinib, and an investigational c-Met inhibitor) | 58 | 0 | 0 | 9 | 0 | 9 |
| Purde et al43 | 61 [41–73] | 6 (54.55) | NSCLC (6), melanoma (5) | Stage 4 | Anti-PD1 (6), CTLA4 (1), anti-PD1 + CTLA4 (3) | 135 | 6 | 4 | 1 | 11 | |
| Ng et al44 | HCC | Stage 4 | 168 | 12 | 12 | 24 | |||||
| Riveiro-Barciela et al45 | 65 [IQR: 56–75] | 11 (47.8) | NSCLC (7), Urinary tract (6), melanoma, (4), endometrial (2), HCC (1), cholangiocarcinoma (1), breast(1) chordoma (1) | Stage 3 (30%) Stage 4 (70%) |
Anti-PD1 or anti–PD-1/PD-L1 (18), anti–CTLA-4 ± anti-PD1 (4), CD40 agonist antibodies (1) | 0 | 0 | 19 | 4 | 23 | |
| Alomari et al46 | Stage 4 | Nivolumab (9), pembrolizumab (7), ipilimumab (1), avelumab (2), nivolumab and ipilimumab (4) | 567 | 8 | 9 | 4 | 2 | 23 | |||
| Miah et al47 | 60 [IQR: 51.9–66.8] | 30 (46.9) | Head and neck (2), melanoma (24), NSCLC + SCLC (9), RCC (7), Other (22) | Stage 4 | PD1 or CTLA monotherapy (46), Combination PD-1 and CTLA-4 (13), other (5) | 1096 | 30 | 34 | 64 | ||
| Hountondji et al48 | 63 [23–89] | 63 (53.8) | Melanoma (49), lung (32), renal (16), urothelial (6), cutaneous and oral SCC (7), GI (3), HCC (2), hematological (1), pancreatic(1) | Stage 1-2 (29%) Stage 3 (16%) Stage 4 (54%) |
Anti–PD-1 (62), anti–PD-L1 (8), anti–CTLA–4 (4), anti–PD-1 + anti–CTLA–4 (42), anti–PD-1 + anti-LAG-3 (1) | 1058 | 4 | 17 | 73 | 23 | 117 |
| Matsukane et al49 | 1008 | 17 | 15 | 33 | 65 | ||||||
| Parlati et al50 | 62 [IQR: 48–73] | 14 (40) | Melanoma (19), lymphoma (1), NSCLC (10), other (5) | Anti–PD-1 monotherapy (26), anti-PD1/anti-CTLA4 (9) | 5 | 7 | 12 | 11 | 35 | ||
| Storm et al51 | 62.1 (16.7) | 55 (56.7) | Head and neck (10), lung (13), skin (42), GI (5), GU (22), sarcoma (4), other (1) | Pembrolizumab (30), nivolumab (13), ipilimumab/nivolumab combination (43), cemiplimab (2), ipilimumab (5), atezolizumab (4) | 2611 | 37 | 46 | 14 | 97 | ||
Age is summarized in median (range), median [IQR Q1-Q3], mean (SD).
Abbreviations: cSCC, cutaneous squamous cell carcinoma; GBM, glioblastoma multiforme; GI, gastrointestinal; GU, genitourinary; HNSCC, head and neck squamous cell carcinoma; ICI, immune checkpoint inhibitor; MM, multiple myeloma; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; RCC, renal cell carcinoma; NSCLC, non-small cell lung cancer.