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 (Cmin) 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 Cmin. During 24-week follow-up, CMV infection incidence was 16.4%. A significant correlation was identified between letermovir Cmin and its clinical efficacy, and the CART model showed an increased risk of CMV infection when Cmin ≤ 2731 ng/mL. However, no clear correlation was found between Cmin and adverse events. Gastrointestinal graft-versus-host disease, cyclosporine Cmin, gender, and concomitant medications, including mycophenolate mofetil, ondansetron, caspofungin, and methylprednisolone, may impact letermovir Cmin. Additionally, coadministration with cyclosporine injection significantly decreased median letermovir Cmin 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 Cmin 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 Cmin.