Work

A simple automated assay format for measuring multiple immune checkpoint inhibitors

Year: 2024

Type: article

Abstract: Immune checkpoint inhibitors (ICIs) have improved survival rates in oncology, but there is a rising concern for immune-related adverse health outcomes. Monitoring drug serum concentration would enable tailored dosing, however this strategy has not yet been evaluated for ICIs. Fully automated analyte capture assays with time-resolved fluorometry using protein A as tracer, were developed for three different ICIs; the cytotoxic T lymphocyte Antigen-4 (CTLA4) inhibitor ipilimumab (Yervoy; Bristol-Myers Squibb) and the Programmed Death-1 (PD-1) inhibitors nivolumab (Opdivo; Bristol-Myers Squibb) and pembrolizumab (Keytruda; Merck). Drug trough levels were measured in serum samples from ICI-treated patients. Measuring ranges were 1–100 mg/L for all three drugs. Automation allowed for 110 samples to be analyzed in < 4 h. Median drug trough-levels after 5–7 weeks of treatment were 20 (range <1.0–45) mg/L for ipilimumab (n = 113), 60 (range 14–75) mg/L) for nivolumab (n = 21) and 19 (range 7.4–39) mg/L for pembrolizumab (n = 20). Routine drug concentration monitoring for ipilimumab, nivolumab and pembrolizumab is feasible using fully automated analyte capture assays constructed with commercially available reagents. The large drug serum concentration ranges in samples from real-world patients, should be further investigated to assess the clinical relevance of ICI concentration monitoring. • Fully automated analyte capture assays with commercially available reagents developed for three immune checkpoint inhibitors. • Routine drug concentration monitoring of the immune checkpoint inhibitors is feasible with this method. • Large drug serum concentration ranges is found in samples from real-world patients.

Source: Journal of Pharmaceutical and Biomedical Analysis

DOI: 10.1016/j.jpba.2024.116657