Related Experiment Video
Updated: Jan 13, 2026
Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
Published on: May 27, 2011
Model-based assessment of letermovir pharmacokinetics in allogeneic haematopoietic stem cell transplant recipients
Chrisoula Tahtsidou1, Sabrina Kraus2, Hartwig Klinker3
1Department of Pharmacy, Ludwig-Maximilians-Universität München, Munich, Germany.
Objectives:
The aim of this retrospective study was to investigate letermovir exposure in allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients under real-world conditions and to evaluate the impact of patient characteristics and comedication on exposure using a population pharmacokinetic (popPK) approach.
Patients And Methods:
Serum samples from allo-HSCT patients receiving oral letermovir were analysed. A population pharmacokinetic model derived from phase III data was adapted to our real-world population, and was used to assess letermovir pharmacokinetics and identify potential covariates.
Results:
Pronounced intra- and interindividual variability was observed across 247 serum samples from 51 allo-HSCT recipients. The medians of observed individual mean minimal letermovir concentrations (Cmin) were 2615 ng/mL in patients receiving LTV 240 mg/day with ciclosporin A (CsA) and 2141 ng/mL in those receiving 480 mg/day without CsA. No correlation was found between Cmin and adverse events. Application of the phase III popPK model yielded considerably higher observed concentrations compared with simulated values. These differences were attributed to a higher systemic availability of letermovir and reduced apparent central volume of distribution in our cohort. Exploratory analyses revealed a 76.5% reduction in relative bioavailability among patients with gastrointestinal graft-versus-host disease (GI GvHD), reflected by a notable decrease in Cmin.
Conclusions:
Our findings support the overall tolerability and efficacy of letermovir in allo-HSCT recipients. Discrepancies between observed and simulated Cmin suggest that the phase III model may underestimate letermovir exposure, underscoring the importance of incorporating real-world data to improve characterization of letermovir pharmacokinetics. Conversely, the decreased exposure observed in a small cohort of GI GvHD patients may compromise efficacy and warrants further investigations to elucidate the impact of GI complications on letermovir exposure.
