Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors
Keywords: 
Pharmacokinetics (PK)
iImmune checkpoint inhibitors (ICIs)
Pharmacodynamics (PD)
Issue Date: 
2019
Publisher: 
Springer Science and Business Media LLC
ISSN: 
1179-1926
Note: 
This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Citation: 
Centanni, M. (Maddalena); Moes, D.J.A.R. (Dirk Jan A. R.); Troconiz, I.F. (Iñaki F.); et al. "Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors". Clinical Pharmacokinetics. 58, 2019, 835 - 857
Abstract
Immune checkpoint inhibitors (ICIs) have demonstrated signifcant clinical impact in improving overall survival of several malignancies associated with poor outcomes; however, only 20–40% of patients will show long-lasting survival. Further clarifcation of factors related to treatment response can support improvements in clinical outcome and guide the development of novel immune checkpoint therapies. In this article, we have provided an overview of the pharmacokinetic (PK) aspects related to current ICIs, which include target-mediated drug disposition and time-varying drug clearance. In response to the variation in treatment exposure of ICIs and the signifcant healthcare costs associated with these agents, arguments for both dose individualization and generalization are provided. We address important issues related to the efcacy and safety, the pharmacodynamics (PD), of ICIs, including exposure–response relationships related to clinical outcome. The unique PK and PD aspects of ICIs give rise to issues of confounding and suboptimal surrogate endpoints that complicate interpretation of exposure–response analysis. Biomarkers to identify patients benefting from treatment with ICIs have been brought forward. However, validated biomarkers to monitor treatment response are currently lacking.

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