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Renal toxicities in immune checkpoint inhibitors with or without chemotherapy: An observational, retrospective, pharmacovigilance study leveraging US FARES database

BACKGROUND: Immune checkpoint inhibitors (ICIs) have elicited durable antitumor responses in multiple types of cancers. However, ICIs could also induce potential toxicities that involve all organs, including renal system. In this study, we aimed to conduct a comprehensive description of the ICIs‐ind...

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Autores principales: Hu, Fangyuan, Zhai, Yinghong, Yuan, Lei, Liang, Jizhou, Xu, Jinfang, Guo, Xiaojing, Zhou, Xiang, Lin, Zhen, Sun, Jinhai, Ye, Xiaofei, He, Jia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8683558/
https://www.ncbi.nlm.nih.gov/pubmed/34845857
http://dx.doi.org/10.1002/cam4.4343
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author Hu, Fangyuan
Zhai, Yinghong
Yuan, Lei
Liang, Jizhou
Xu, Jinfang
Guo, Xiaojing
Zhou, Xiang
Lin, Zhen
Sun, Jinhai
Ye, Xiaofei
He, Jia
author_facet Hu, Fangyuan
Zhai, Yinghong
Yuan, Lei
Liang, Jizhou
Xu, Jinfang
Guo, Xiaojing
Zhou, Xiang
Lin, Zhen
Sun, Jinhai
Ye, Xiaofei
He, Jia
author_sort Hu, Fangyuan
collection PubMed
description BACKGROUND: Immune checkpoint inhibitors (ICIs) have elicited durable antitumor responses in multiple types of cancers. However, ICIs could also induce potential toxicities that involve all organs, including renal system. In this study, we aimed to conduct a comprehensive description of the ICIs‐induced renal toxicities and the potential effects of chemotherapy. METHODS: We conducted a pharmacovigilance study based on US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database between 01 January 2014 and 30 June 2019. Disproportionality analysis was used to assess the association between ICIs and renal adverse events (AEs), including reporting odds ratio (ROR) and information component (IC). ROR(025) and IC(025) are, respectively, 95% confidence interval lower end of ROR and IC. If the value of ROR(025) exceeding one or IC(025) higher than zero, then a signal was considered statistically significant. RESULTS: A total of 30,602,758 reports were extracted from the database, with 4578 reports for ICIs‐associated renal AEs. Renal AEs were more frequently reported in anti‐PD‐1/PD‐L1 versus anti‐CTLA‐4 monotherapy group (ROR: 1.75, 95% CI: 1.52–2.01). Similarly, renal AEs were more commonly reported in ICIs polytherapy other than monotherapy group (ROR: 1.18, 95% CI: 1.10–1.27). Notably, ICIs plus chemotherapy strategies reported more renal toxicities compared to sole ICIs regimens (ROR: 1.30, 95% CI: 1.17–1.45), whereas exhibited lower fatality outcome rates. Importantly, acute kidney injury (1139, 24.88%) and renal failure (464, 10.14%) were the top two most commonly reported ICIs‐associated renal AEs, and also observed with the top two highest level of fatality outcome rates. CONCLUSIONS: A spectrum of renal AEs was detected in ICIs regimens and could be reinforced by ICIs combination. Compared to sole ICIs regimens, ICIs plus chemotherapy strategy reported more renal toxicities but lower fatality outcome rates. With the increasing popularity of ICIs especially combination strategies, it is vital important for clinicians to guarantee balance between durable clinical effects and potential renal toxicities in latest immunotherapy strategies.
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spelling pubmed-86835582021-12-30 Renal toxicities in immune checkpoint inhibitors with or without chemotherapy: An observational, retrospective, pharmacovigilance study leveraging US FARES database Hu, Fangyuan Zhai, Yinghong Yuan, Lei Liang, Jizhou Xu, Jinfang Guo, Xiaojing Zhou, Xiang Lin, Zhen Sun, Jinhai Ye, Xiaofei He, Jia Cancer Med Clinical Cancer Research BACKGROUND: Immune checkpoint inhibitors (ICIs) have elicited durable antitumor responses in multiple types of cancers. However, ICIs could also induce potential toxicities that involve all organs, including renal system. In this study, we aimed to conduct a comprehensive description of the ICIs‐induced renal toxicities and the potential effects of chemotherapy. METHODS: We conducted a pharmacovigilance study based on US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database between 01 January 2014 and 30 June 2019. Disproportionality analysis was used to assess the association between ICIs and renal adverse events (AEs), including reporting odds ratio (ROR) and information component (IC). ROR(025) and IC(025) are, respectively, 95% confidence interval lower end of ROR and IC. If the value of ROR(025) exceeding one or IC(025) higher than zero, then a signal was considered statistically significant. RESULTS: A total of 30,602,758 reports were extracted from the database, with 4578 reports for ICIs‐associated renal AEs. Renal AEs were more frequently reported in anti‐PD‐1/PD‐L1 versus anti‐CTLA‐4 monotherapy group (ROR: 1.75, 95% CI: 1.52–2.01). Similarly, renal AEs were more commonly reported in ICIs polytherapy other than monotherapy group (ROR: 1.18, 95% CI: 1.10–1.27). Notably, ICIs plus chemotherapy strategies reported more renal toxicities compared to sole ICIs regimens (ROR: 1.30, 95% CI: 1.17–1.45), whereas exhibited lower fatality outcome rates. Importantly, acute kidney injury (1139, 24.88%) and renal failure (464, 10.14%) were the top two most commonly reported ICIs‐associated renal AEs, and also observed with the top two highest level of fatality outcome rates. CONCLUSIONS: A spectrum of renal AEs was detected in ICIs regimens and could be reinforced by ICIs combination. Compared to sole ICIs regimens, ICIs plus chemotherapy strategy reported more renal toxicities but lower fatality outcome rates. With the increasing popularity of ICIs especially combination strategies, it is vital important for clinicians to guarantee balance between durable clinical effects and potential renal toxicities in latest immunotherapy strategies. John Wiley and Sons Inc. 2021-11-29 /pmc/articles/PMC8683558/ /pubmed/34845857 http://dx.doi.org/10.1002/cam4.4343 Text en © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Cancer Research
Hu, Fangyuan
Zhai, Yinghong
Yuan, Lei
Liang, Jizhou
Xu, Jinfang
Guo, Xiaojing
Zhou, Xiang
Lin, Zhen
Sun, Jinhai
Ye, Xiaofei
He, Jia
Renal toxicities in immune checkpoint inhibitors with or without chemotherapy: An observational, retrospective, pharmacovigilance study leveraging US FARES database
title Renal toxicities in immune checkpoint inhibitors with or without chemotherapy: An observational, retrospective, pharmacovigilance study leveraging US FARES database
title_full Renal toxicities in immune checkpoint inhibitors with or without chemotherapy: An observational, retrospective, pharmacovigilance study leveraging US FARES database
title_fullStr Renal toxicities in immune checkpoint inhibitors with or without chemotherapy: An observational, retrospective, pharmacovigilance study leveraging US FARES database
title_full_unstemmed Renal toxicities in immune checkpoint inhibitors with or without chemotherapy: An observational, retrospective, pharmacovigilance study leveraging US FARES database
title_short Renal toxicities in immune checkpoint inhibitors with or without chemotherapy: An observational, retrospective, pharmacovigilance study leveraging US FARES database
title_sort renal toxicities in immune checkpoint inhibitors with or without chemotherapy: an observational, retrospective, pharmacovigilance study leveraging us fares database
topic Clinical Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8683558/
https://www.ncbi.nlm.nih.gov/pubmed/34845857
http://dx.doi.org/10.1002/cam4.4343
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