Role of letermovir therapeutic drug monitoring for cytomegalovirus prophylaxis in allogeneic hematopoietic stem cell transplantation recipients: a prospective study.

Purpose: The role of therapeutic drug monitoring (TDM) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients receiving letermovir has not yet been clarified. This study is to explore letermovir trough concentration (C_min) correlation with its clinical efficacy and adverse events, and factors affecting its plasma concentrations.

Methods: A prospective, non-interventional study was performed in allo-HSCT recipients receiving letermovir prophylaxis. Plasma concentrations were determined using high-performance liquid chromatography-tandem mass spectrometry. Data analysis was performed using logistic regression, linear regression, and classification and regression tree (CART) models.

Results: 701 trough concentrations from 71 recipients were included, uncovering pronounced intra- and inter-individual variability in letermovir C_min. During 24-week follow-up, CMV infection incidence was 16.4%. A significant correlation was identified between letermovir C_min and its clinical efficacy, and the CART model showed an increased risk of CMV infection when C_min ≤ 2731 ng/mL. However, no clear correlation was found between C_min and adverse events. Gastrointestinal graft-versus-host disease, cyclosporine C_min, gender, and concomitant medications, including mycophenolate mofetil, ondansetron, caspofungin, and methylprednisolone, may impact letermovir C_min. Additionally, coadministration with cyclosporine injection significantly decreased median letermovir C_min compared with cyclosporine capsules (2311 vs. 3386 ng/mL). Moreover, with the extension of time post-transplant, trough concentrations of both cyclosporine and letermovir significantly decreased.

Conclusion: TDM for letermovir may be beneficial in allo-HSCT recipients considering the variability in letermovir C_min and its correlation with clinical efficacy. Moreover, drug interactions and the effects of changes in cyclosporine dosage forms or concentrations require careful monitoring for their effect on letermovir C_min.