Towards Therapeutic Drug Monitoring of Immune Checkpoint Inhibitors in Solid Tumours? A Scoping Review

Abstract

Background: Immune checkpoint inhibitors (ICIs) have revolutionised the management of solid tumours by targeting immune evasion pathways and enhancing immune responses against tumours. Although effective, the variable response rates and potential for severe immune- related adverse events (irAEs) are a limitation of ICIs. This underscores the need for predictive tools to optimise clinical outcomes. Therapeutic Drug Monitoring (TDM), which involves measuring drug concentrations or monitoring anti-drug antibodies (ADA), could offer a promising approach to personalise therapy and enhance the safety and efficacy of ICIs. This review assesses the current scope of evidence linking drug concentrations and anti-drug antibodies with clinical outcomes in the context of TDM. Methods: This review used a comprehensive search strategy across several electronic databases, including PubMed, Medline, Embase, and Web of Science, focusing on articles published from inception until June 24, 2024. Studies included in the review met specific criteria, such as containing original human data on approved ICIs for solid tumours and reporting relevant pharmacokinetic data and clinical outcomes. Data extraction followed a standardised form, and a narrative synthesis approach was employed to describe and analyse the findings. Results: Out of 7,663 references initially identified, 40 met the inclusion criteria. These studies predominantly analysed the impact of drug concentration on clinical outcomes (30/40 studies), the effect of anti-drug antibodies on clinical outcomes (8/40 studies), and the combined impact of drug concentrations and anti-drug antibodies on outcomes (2/40 studies). The studies reviewed covered nine of the twelve approved ICIs. The bioanalytical assay used to detect drug concentration varied across the references, and 12 publications did not report the type of bioanalytical assay used. Ipilimumab shows the most consistent evidence of an exposure-response relationship. Conclusions: Current knowledge of drug concentration and clinical efficacy for ICI generally demonstrates a flat relationship between drug concentration and clinical outcome. However, promising evidence linking clearance to clinical outcomes needs to be evaluated. In ADA, the current scope of knowledge is limited to determining a relationship with the clinical outcome.