Therapeutic drug monitoring of letermovir in allogeneic hematopoietic cell transplant recipients: where are we?

INTRODUCTION: Letermovir is an antiviral licensed for the prophylaxis of cytomegalovirus (CMV) infection in CMV seropositive allogeneic hematopoietic stem cell transplant (HSCT) recipients. Unlike other anti-CMV agents, letermovir has a favorable toxicity profile. Although the efficacy of letermovir in preventing CMV infection has been demonstrated in clinical trials, virologic failure may occur possibly due to suboptimal letermovir concentrations. AREAS COVERED: This review summarizes the pharmacology of letermovir with emphasis on factors that can impact letermovir exposure including drug-drug interactions in a population frequently on multiple medications. Studies on letermovir exposure-response relationship are summarized, and the role of therapeutic drug monitoring (TDM) is discussed. A PubMed search using the terms: 'letermovir' and the following terms 'pharmacodynamics,' 'resistances,' 'pharmacokinetics,' 'drug-drug interactions, 'therapeutic drug monitoring' were used to compile data until November 2025. EXPERT OPINION: Letermovir meets several criteria for TDM, including large interindividual pharmacokinetic variability and exposure-response relationship, albeit, the latter has not been consistently demonstrated. Randomized controlled trials are needed to determine the clinical benefit of letermovir TDM in HSCT recipients. Furthermore, studies are warranted to characterize letermovir pharmacokinetics in situations encountered in clinical practice (complex drug-drug interactions and/or organ dysfunction) and to determine letermovir optimal dosing in the pediatric population.