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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Detalles Bibliográficos
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
Descripción
Sumario: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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