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Population pharmacokinetic models of anti-PD-1 mAbs in patients with multiple tumor types: A systematic review

AIMS AND BACKGROUND: A number of population pharmacokinetic (PPK) models of anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAbs) in multiple tumor types have been published to characterize the influencing factors of their pharmacokinetics. This review described PPK models of anti-PD-1 mA...

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Autores principales: Shang, Jingyuan, Huang, Lin, Huang, Jing, Ren, Xiaolei, Liu, Yi, Feng, Yufei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379304/
https://www.ncbi.nlm.nih.gov/pubmed/35983041
http://dx.doi.org/10.3389/fimmu.2022.871372
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author Shang, Jingyuan
Huang, Lin
Huang, Jing
Ren, Xiaolei
Liu, Yi
Feng, Yufei
author_facet Shang, Jingyuan
Huang, Lin
Huang, Jing
Ren, Xiaolei
Liu, Yi
Feng, Yufei
author_sort Shang, Jingyuan
collection PubMed
description AIMS AND BACKGROUND: A number of population pharmacokinetic (PPK) models of anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAbs) in multiple tumor types have been published to characterize the influencing factors of their pharmacokinetics. This review described PPK models of anti-PD-1 mAbs that investigate the magnitude and types of covariate effects in PK parameters, provide a reference for building PPK models of other anti-PD-1 mAbs, and identify areas requiring additional research to facilitate the application of PPK models. METHODS: A systematic search for analyses of PPK models of eleven anti-PD-1 mAbs on the market that were carried out in humans was conducted using PubMed, Embase, and the Cochrane Library. The search covered the period from the inception of the databases to April 2022. RESULTS: Currently, there are fourteen analyses on PPK models of anti-PD-1 mAbs summarized in this review, including seven models that refer to nivolumab, four referring to pembrolizumab, one referring to cemiplimab, one referring to camrelizumab, and one referred to dostarlimab. Most analyses described the pharmacokinetics of anti-PD-1 mAbs with a two-compartment model with time-varying clearance (CL) and a sigmoidal maximum effect. The estimated CL and volume of distribution in the central (V(C)) ranged from 0.179 to 0.290 L/day and 2.98 to 4.46 L, respectively. The median (range) of interindividual variability (IIV) for CL and V(C) was 30.9% (8.7%–50.8%) and 29.0% (4.32%–40.7%), respectively. The commonly identified significant covariates were body weight (BW) on CL and V(C), and albumin (ALB), tumor type, sex, and performance status (PS) on CL. Other less assessed significant covariates included lactate dehydrogenase (LDH), immunoglobulin G (IgG), ipilimumab coadministration (IPICO) on CL, and body mass index (BMI), malignant pleural mesothelioma (MESO) on V(C). CONCLUSION: This review provides detailed information about the characteristics of PPK models of anti-PD-1 mAbs, the effects of covariates on PK parameters, and the current status of the application of the models. ALB, BW, specific tumor type, sex, and PS should be considered for the future development of the PPK model of anti-PD-1 mAbs. Other potential covariates that were assessed less frequently but still have significance (e.g., LDH, IgG, and IPICO) should not be ignored. Thus, further research and thorough investigation are needed to assess new or potential covariates, which will pave the way for personalized anti-PD-1 mAbs therapy.
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spelling pubmed-93793042022-08-17 Population pharmacokinetic models of anti-PD-1 mAbs in patients with multiple tumor types: A systematic review Shang, Jingyuan Huang, Lin Huang, Jing Ren, Xiaolei Liu, Yi Feng, Yufei Front Immunol Immunology AIMS AND BACKGROUND: A number of population pharmacokinetic (PPK) models of anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAbs) in multiple tumor types have been published to characterize the influencing factors of their pharmacokinetics. This review described PPK models of anti-PD-1 mAbs that investigate the magnitude and types of covariate effects in PK parameters, provide a reference for building PPK models of other anti-PD-1 mAbs, and identify areas requiring additional research to facilitate the application of PPK models. METHODS: A systematic search for analyses of PPK models of eleven anti-PD-1 mAbs on the market that were carried out in humans was conducted using PubMed, Embase, and the Cochrane Library. The search covered the period from the inception of the databases to April 2022. RESULTS: Currently, there are fourteen analyses on PPK models of anti-PD-1 mAbs summarized in this review, including seven models that refer to nivolumab, four referring to pembrolizumab, one referring to cemiplimab, one referring to camrelizumab, and one referred to dostarlimab. Most analyses described the pharmacokinetics of anti-PD-1 mAbs with a two-compartment model with time-varying clearance (CL) and a sigmoidal maximum effect. The estimated CL and volume of distribution in the central (V(C)) ranged from 0.179 to 0.290 L/day and 2.98 to 4.46 L, respectively. The median (range) of interindividual variability (IIV) for CL and V(C) was 30.9% (8.7%–50.8%) and 29.0% (4.32%–40.7%), respectively. The commonly identified significant covariates were body weight (BW) on CL and V(C), and albumin (ALB), tumor type, sex, and performance status (PS) on CL. Other less assessed significant covariates included lactate dehydrogenase (LDH), immunoglobulin G (IgG), ipilimumab coadministration (IPICO) on CL, and body mass index (BMI), malignant pleural mesothelioma (MESO) on V(C). CONCLUSION: This review provides detailed information about the characteristics of PPK models of anti-PD-1 mAbs, the effects of covariates on PK parameters, and the current status of the application of the models. ALB, BW, specific tumor type, sex, and PS should be considered for the future development of the PPK model of anti-PD-1 mAbs. Other potential covariates that were assessed less frequently but still have significance (e.g., LDH, IgG, and IPICO) should not be ignored. Thus, further research and thorough investigation are needed to assess new or potential covariates, which will pave the way for personalized anti-PD-1 mAbs therapy. Frontiers Media S.A. 2022-08-02 /pmc/articles/PMC9379304/ /pubmed/35983041 http://dx.doi.org/10.3389/fimmu.2022.871372 Text en Copyright © 2022 Shang, Huang, Huang, Ren, Liu and Feng https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Shang, Jingyuan
Huang, Lin
Huang, Jing
Ren, Xiaolei
Liu, Yi
Feng, Yufei
Population pharmacokinetic models of anti-PD-1 mAbs in patients with multiple tumor types: A systematic review
title Population pharmacokinetic models of anti-PD-1 mAbs in patients with multiple tumor types: A systematic review
title_full Population pharmacokinetic models of anti-PD-1 mAbs in patients with multiple tumor types: A systematic review
title_fullStr Population pharmacokinetic models of anti-PD-1 mAbs in patients with multiple tumor types: A systematic review
title_full_unstemmed Population pharmacokinetic models of anti-PD-1 mAbs in patients with multiple tumor types: A systematic review
title_short Population pharmacokinetic models of anti-PD-1 mAbs in patients with multiple tumor types: A systematic review
title_sort population pharmacokinetic models of anti-pd-1 mabs in patients with multiple tumor types: a systematic review
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379304/
https://www.ncbi.nlm.nih.gov/pubmed/35983041
http://dx.doi.org/10.3389/fimmu.2022.871372
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