Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis

Programmed cell death-1 (PD-1) and/or cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) immune checkpoint inhibitor (ICI) treatments are associated with adverse events (AEs), which may be dependent on ICI dose. Applying a model-based meta-analysis to evaluate safety data from published clinical t...

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Autores principales: Shulgin, Boris, Kosinsky, Yuri, Omelchenko, Andrey, Chu, Lulu, Mugundu, Ganesh, Aksenov, Sergey, Pimentel, Rodrigo, DeYulia, Garrett, Kim, Geoffrey, Peskov, Kirill, Helmlinger, Gabriel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Review
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466858/
https://www.ncbi.nlm.nih.gov/pubmed/32934874
http://dx.doi.org/10.1080/2162402X.2020.1748982
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author Shulgin, Boris
Kosinsky, Yuri
Omelchenko, Andrey
Chu, Lulu
Mugundu, Ganesh
Aksenov, Sergey
Pimentel, Rodrigo
DeYulia, Garrett
Kim, Geoffrey
Peskov, Kirill
Helmlinger, Gabriel
author_facet Shulgin, Boris
Kosinsky, Yuri
Omelchenko, Andrey
Chu, Lulu
Mugundu, Ganesh
Aksenov, Sergey
Pimentel, Rodrigo
DeYulia, Garrett
Kim, Geoffrey
Peskov, Kirill
Helmlinger, Gabriel
author_sort Shulgin, Boris
collection PubMed
description Programmed cell death-1 (PD-1) and/or cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) immune checkpoint inhibitor (ICI) treatments are associated with adverse events (AEs), which may be dependent on ICI dose. Applying a model-based meta-analysis to evaluate safety data from published clinical trials from 2005 to 2018, we analyzed the dose/exposure dependence of ICI treatment-related AE (trAE) and immune-mediated AE (imAE) rates. Unlike with PD-1 inhibitor monotherapy, CTLA-4 inhibitor monotherapy exhibited a dose/exposure dependence on most AE types evaluated. Furthermore, combination therapy with PD-1 inhibitor significantly strengthened the dependence of trAE and imAE rates on CTLA-4 inhibitor dose/exposure.
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spelling pubmed-74668582020-09-14 Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis Shulgin, Boris Kosinsky, Yuri Omelchenko, Andrey Chu, Lulu Mugundu, Ganesh Aksenov, Sergey Pimentel, Rodrigo DeYulia, Garrett Kim, Geoffrey Peskov, Kirill Helmlinger, Gabriel Oncoimmunology Review Programmed cell death-1 (PD-1) and/or cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) immune checkpoint inhibitor (ICI) treatments are associated with adverse events (AEs), which may be dependent on ICI dose. Applying a model-based meta-analysis to evaluate safety data from published clinical trials from 2005 to 2018, we analyzed the dose/exposure dependence of ICI treatment-related AE (trAE) and immune-mediated AE (imAE) rates. Unlike with PD-1 inhibitor monotherapy, CTLA-4 inhibitor monotherapy exhibited a dose/exposure dependence on most AE types evaluated. Furthermore, combination therapy with PD-1 inhibitor significantly strengthened the dependence of trAE and imAE rates on CTLA-4 inhibitor dose/exposure. Taylor & Francis 2020-05-21 /pmc/articles/PMC7466858/ /pubmed/32934874 http://dx.doi.org/10.1080/2162402X.2020.1748982 Text en © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Shulgin, Boris
Kosinsky, Yuri
Omelchenko, Andrey
Chu, Lulu
Mugundu, Ganesh
Aksenov, Sergey
Pimentel, Rodrigo
DeYulia, Garrett
Kim, Geoffrey
Peskov, Kirill
Helmlinger, Gabriel
Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis
title Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis
title_full Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis
title_fullStr Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis
title_full_unstemmed Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis
title_short Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis
title_sort dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466858/
https://www.ncbi.nlm.nih.gov/pubmed/32934874
http://dx.doi.org/10.1080/2162402X.2020.1748982
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