| アブストラクト | BACKGROUND: Solid organ transplant recipients are at increased risk of cancer due to long-term immunosuppression. Immune-checkpoint inhibitors (ICI) showed clinical benefits but increased risk of transplant rejection. Our work aims to assess the main features of reported rejection events. METHODS: A disproportionality analysis of the World Health Organisation pharmacovigilance database, VigiBase, to identify drugs associated with rejection events. The estimate of this analysis is the information component for which the lower end of the 95% credibility interval (IC025) indicates significance when positive. We combined a systematic literature review of case reports to obtain additional information regarding treatment management and histopathological findings. RESULTS: A total of 96 reports of transplant rejections following ICI were included, including kidney (n = 65), liver (n = 23), cornea (n = 2) and heart (n = 5). The main indication reported for ICI was malignant melanoma (39/89, 43.8%). The time to onset between first ICI administration and rejection was 21 [interquartile range: 13; 56] days. Kidney transplant rejection was associated with nivolumab (IC025 = 1.32), pembrolizumab (IC025 = 1.17) and ipilimumab (IC025 = 0.33); while liver transplant rejection was mostly over-reported with nivolumab (IC025 = 1.95). Overall, anti-PD-1 and anti-PD-L1 were more involved than anti-CTLA-4 drugs (93.0% versus 7.0%). Subsequent mortality was 36.5% and involved liver-transplant recipients more than other organ recipients (p < 0.0001). When performed, all biopsies reported acute cellular rejections, but only a few showed concomitant antibody-mediated lesions (6/28, 21.4%). Management mainly consisted in intravenous corticosteroid boluses and ICI cessation. CONCLUSION: ICI-associated transplant rejections were mostly reported in kidney and liver transplant recipients. Rejections were T-cell mediated with low participation of humoral response. |
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| 投稿者 | Nguyen, Lee S; Ortuno, Sofia; Lebrun-Vignes, Benedicte; Johnson, Douglas B; Moslehi, Javid J; Hertig, Alexandre; Salem, Joe-Elie |
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| 組織名 | Sorbonne University, INSERM CIC Paris-Est, AP-HP, ICAN, Regional;Pharmacovigilance Centre, Pitie-Salpetriere Hospital, Department of Pharmacology,;F-75013 Paris, France; CMC Ambroise Pare, Research & Innovation (RICAP),;Neuilly-sur-Seine, France. Electronic address: nguyen.lee@icloud.com.;AP.HP.5 Cochin, Intensive Care Medicine Department, F-75014, France.;F-75013 Paris, France; Universite Paris Est Creteil, EpiDermE, F-94010, Creteil,;France.;Departments of Medicine and Pharmacology, Cardio-oncology Program, Vanderbilt;University Medical Center, Nashville, TN, USA.;Sorbonne University, Department of Nephrology, AP.HP.6 Pitie-Salpetriere, France.;F-75013 Paris, France; Departments of Medicine and Pharmacology, Cardio-oncology;Program, Vanderbilt University Medical Center, Nashville, TN, USA. |
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