Long-Term Monitoring of Everolimus Concentrations in Routine Clinical Practice: Evaluation of Patient Percentiles as Quality Indicator and Impact of Analytical Method Change

Abstract

Background: Everolimus, an mTOR inhibitor used in oncology and organ transplantation, requires therapeutic drug monitoring due to the narrow therapeutic range of everolimus and substantial pharmacokinetic variation. Patient-derived data can function as a supplementary quality indicator for laboratory methods by providing real-world information on analytical performance. Methods: All routine whole-blood everolimus measurements performed at Akademiska University Hospital, Uppsala, Sweden, 2012 to 2025 were retrospectively evaluated. In total, 9,089 results were included. Annual and monthly concentration distributions were assessed using the 10th, 25th, 50th, 75th, and 90th percentiles. Long-term trends, sex differences, seasonal variation, and the impact of a method change from Architect (Abbott/Microgenics) to Cobas Pro e 801 (Roche) in 2021 were investigated. Results: Of 9089 results, 3335 were from females and 5754 from males. Concentration distributions were similar between sexes, with median concentrations of 4.47 and 4.33 µg/L, respectively; the overall median was 4.37 µg/L. Annual testing volumes remained stable. Median concentrations gradually declined from 5.22 µg/L in 2012 to approximately 4.0 µg/L in 2019–2020. Following introduction of the Cobas assay, patient concentration distributions shifted upward; compared with 2020, the 10th percentile increased by 45%, the median by 21%, and the 90th percentile by 11%. External quality assessment and method-comparison studies supported an analytical explanation. Conclusions: Everolimus concentration distributions were stable over time and showed no meaningful sex-related or seasonal variation. Patient percentile monitoring detected a clear analytical shift after method implementation and may serve as a practical supplementary quality indicator for TDM assays.