TABLE 3.
Characteristics of 89 cases allograft rejection in SOTRs from literature review
| Characteristics | No (%) | Ipilimumab | Nivolumab | Pembrolizumab | Cemiplimab | Toripalimab | Sequential b | Combination (Nivolumab + Ipilimumab) |
|---|---|---|---|---|---|---|---|---|
| Total | 89 a | 6 (6.74%) | 34 (38.2%) | 32 (35.96%) | 6 (6.74%) | 1 (1.12%) | 5 (5.62%) | 4 (4.49%) |
| Median age (range), years | 63 (14–85) | 63.5 (40–72) | 62.5 (14–84) | 63.5 (29–85) | 64.5 (51–84) | 62 (62) | 52 (48–68) | 58 (40–72) |
| Gender | ||||||||
| Male | 61 (68.54%) | 3 | 23 | 21 | 4 | 5 | 4 | |
| Female | 28 (31.46%) | 3 | 11 | 11 | 2 | 1 | ||
| Rejection (allograft failure) | ||||||||
| Kidney | 60 (67.42%) | 4 (2) | 19 (4) | 21 (4) | 6 (1) | 5 (1) | 4 (0) | |
| Liver | 19 (21.35%) | 1 (0) | 11 (7) | 6 (0) | 1 (1) | |||
| Heart | 5 (5.62%) | 2 (2) | 3 (2) | |||||
| Cornea | 3 (3.37%) | 1 (0) | 1 (0) | 1 (0) | ||||
| Lung | 1 (1.12%) | 1 (1) | ||||||
| Pancreas + Kidney | 1 (1.12%) | 1 (0) | ||||||
| Type of cancer | ||||||||
| MM | 37 (41.57%) | 5 | 9 | 15 | 5 | 2 | ||
| HCC | 10 (11.24%) | 7 | 2 | 1 | ||||
| cSCC | 9 (10.11%) | 1 | 4 | 3 | 1 | |||
| SCC | 8 (8.99%) | 4 | 2 | 2 | ||||
| RCC | 5 (5.62%) | 5 | ||||||
| UCC | 4 (4.49%) | 1 | 2 | 1 | ||||
| NSCLC | 6 (6.74%) | 5 | 1 | |||||
| Others | 10 (11.24%) | 1 | 2 | 6 | 1 | |||
| Time from Transplantation to Immunotherapy, median (range), years | 10 (0.2–43.2) | 15.5 (1.5–19) | 5.75 (0.7–26.5) | 12.4 (0.2–32) | 17 (7–43.2) | 1.9 (1.9) | 14 (5–15) | 5.5 (4–7.8) |
| Time from Immunotherapy to Rejection, median (range), days | 20 (2–224) | 20.5 (14–27) | 14 (2–168) | 45.5 (5–224) | 13.5 (4–63) | 7 (7) | 60 (18–119) | 28 (8–28) |
| Number of doses, median (range) | 1.5 (1–14) | 1 (1–4) | 1 (1–14) | 2 (1–11) | 2.5 (1–7) | 1 (1) | 3 (2–5) | 1 (1–2) |
| Immunesuppression at time of initiation of immunotherapy | ||||||||
| Single agent | 40 (44.94%) | |||||||
| Steroids | 25 (28.09%) | 4 | 4 | 10 | 3 | 4 | ||
| Sirolimus | 5 (5.62%) | 1 | 3 | 1 | ||||
| CSA | 2 (3.37%) | 2 | ||||||
| MMF | 2 (2.25%) | 2 | ||||||
| Everolimus | 2 (2.25%) | 1 | ||||||
| Tacrolimus | 3 (3.37%) | 2 | 1 | |||||
| Sirolimus or Everolimus | 1 (1.12%) | 1 | ||||||
| Combination | 32 (35.96%) | |||||||
| 2 drugs combination | 25 (28.09%) | 1 | 10 | 10 | 2 | 1 | 1 | |
| 3 frugs combination | 6 (6.74%) | 3 | 2 | 1 | ||||
| 4 drugs combination | 1 (1.12%) | 1 | ||||||
| Tacrolimus alone or in combination | 19 (21.35%) | 10 | 6 | 2 | 1 | |||
| Steroids alone or in combination | 45 (49.44%) | 5 | 12 | 17 | 6 | 4 | 1 | |
| No Immunesuppression | 5 (5.62%) | 2 | 2 | 1 | ||||
| N/A | 12 (13.48%) | 7 | 3 | 2 | ||||
| Immune checkpoint expression | ||||||||
| Graft positive | 7 (7.87%) | 4 | 2 | 1 | ||||
| Graft negative | 1 (1.12%) | 1 | ||||||
| Tumor positive | 1 (1.12%) | 1 | ||||||
| Tumor negative | 1 (1.12%) | 1 | ||||||
| Graft + Tumor positive | 2 (2.25%) | 1 | 1 | |||||
| N/A | 77 (86.52%) | 6 | 26 | 29 | 6 | 5 | 4 | |
| Prior history of significant rejection | ||||||||
| Yes | 5 (5.62%) | 1 | 4 | |||||
| No | 62 (69.66%) | 4 | 26 | 19 | 3 | 1 | 5 | 3 |
| N/A | 22 (24.72%) | 1 | 4 | 13 | 3 | 1 | ||
| Type of Rejection (biopsy) | ||||||||
| Acute cellular rejection | 29 (32.58%) | 3 | 11 | 8 | 2 | 3 | 1 | |
| Mixed acute cellular and antibody mediated rejection | 13 (14.61%) | 6 | 3 | 1 | 1 | 2 | ||
| Acute and chronic cellular rejection | 2 (2.25%) | 2 | ||||||
| Acute cellular rejection (5 days) Antibody mediated rejection (7 m) | 1 (1.12%) | 1 | ||||||
| Acute cellular rejection (32 days) Antibody mediated rejection (100 days) | 1 (1.12%) | 1 | ||||||
| Acute antibody mediated rejection | 1 (1.12%) | 1 | ||||||
| No Biopsy | 10 (11.24%) | 1 | 5 | 2 | 2 | |||
| N/A | 32 (35.96%) | 2 | 11 | 15 | 1 | 1 | 1 | 1 |
| Response to therapy | ||||||||
| Response rate (CR + PR) | 23 (25.84%) | 0 | 8 | 10 | 0 | 0 | 3 | 2 |
| CR | 9 (10.11%) | 2 | 5 | 1 | 1 | |||
| PR | 14 (15.73%) | 6 | 5 | 2 | 1 | |||
| SD | 6 (6.74%) | 1 | 2 | 2 | 1 | |||
| PD | 31 (34.83%) | 5 | 13 | 8 | 3 | 1 | ||
| N/A | 29 (32.58%) | 1 | 12 | 12 | 1 | 1 | 1 | 1 |
| Outcome | ||||||||
| Live | 33 (37.08%) | 1 | 8 | 17 | 2 | 3 | 2 | |
| Death | 40 (44.94%) | 5 | 19 | 10 | 3 | 1 | 1 | |
| Allograft failure | 26 (29.21%) | 2 | 13 | 7 | 1 | 1 | 1 | |
| N/A | 16 (17.98%) | 7 | 5 | 1 | 2 | 1 | ||
Abbreviations: AZA, azathioprine; CNI, calcineurin inhibitor; CSA, ciclosporin A; CR, complete response; MM, malignant melanoma; HCC, hepatocellular carcinoma; cSCC, cutaneous squamous cell carcinomas; NSCLC, non‐small cell lung cancer; SCC, squamous cell carcinomas; RCC, renal cell carcinoma; UCC, urothelial cell cancer; MMF, mycophenolate mofetil; mTOR inhibitors, mammalian target of rapamycin inhibitor; PD, progressive disease; PR, partial response; SD, stable disease.
a
One patient with an unclear drug, anti‐pd‐1, kidney failure.
b
Pembrolizumab followed by nivolumab (1), ipilimumab followed by pembrolizumab (3), Ipilimumab followed by nivolumab (1).