A simple automated assay format for measuring multiple immune checkpoint inhibitors

Area of Science:

• Pharmacology
• Oncology
• Immunology

Background:

• Immune checkpoint inhibitors (ICIs) enhance cancer survival but raise concerns about immune-related adverse events.
• Tailored dosing via drug serum concentration monitoring is a potential strategy for ICIs, but has not been evaluated.
• Developing reliable assays for ICI drug levels is crucial for clinical application.

Purpose of the Study:

• To develop and evaluate fully automated assays for measuring serum concentrations of three ICIs: ipilimumab, nivolumab, and pembrolizumab.
• To assess the feasibility of routine drug concentration monitoring for these ICIs in patients undergoing treatment.

Main Methods:

• Development of fully automated analyte capture assays utilizing time-resolved fluorometry and protein A tracer.
• Measurement of drug trough levels in serum samples from patients treated with ipilimumab, nivolumab, or pembrolizumab.
• Assays demonstrated measuring ranges of 1-100 mg/L and analyzed 110 samples in under 4 hours.

Main Results:

• Median drug trough-levels after 5-7 weeks were: ipilimumab 20 mg/L (n=113), nivolumab 60 mg/L (n=21), and pembrolizumab 19 mg/L (n=20).
• Observed wide ranges in drug serum concentrations across real-world patient samples.
• The automated assays proved feasible for routine monitoring using commercially available reagents.

Conclusions:

• Routine drug concentration monitoring for ipilimumab, nivolumab, and pembrolizumab is feasible with the developed automated assays.
• The significant variability in serum drug concentrations warrants further investigation into the clinical relevance of ICI monitoring.
• This work supports the potential for personalized dosing strategies in ICI therapy.