Highlights
- •Disproportionality analysis of VigiBase was combined with the literature search.
- •It yielded an association between immune-checkpoint inhibitors and rejection events.
- •Kidney and liver rejections were more reported than other types of organs.
- •Subsequent mortality was 36.5%.
- •T-cell mediated rejection after immunosuppression decrease was common.
Abstract
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.
Keywords
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Article info
Publication history
Published online: March 12, 2021
Accepted:
January 29,
2021
Received in revised form:
December 25,
2020
Received:
July 8,
2020
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
