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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
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.