Characterization of Letermovir Use and Pharmacokinetic Interaction with Immunosuppression in Lung Transplant Recipients

Abstract

<h3>Purpose</h3> Cytomegalovirus (CMV) is a common complication in lung transplant recipients (LTRs). Traditional agents to treat and prevent CMV carry significant toxicities. Prior studies of the CMV-active antiviral letermovir have described pharmacokinetic interactions with immunosuppressive medications, but the LTR population has not routinely been included in these studies and clinical relevance remains unclear. <h3>Methods</h3> This single-center retrospective study included 16 LTRs transplanted between 12/1/2016-7/31/2020 initiated on letermovir while on calcineurin inhibitor and/or mTOR inhibitor-based immunosuppression. Dose-adjusted immunosuppression troughs (concentration/dose or C/D ratios) were collected at baseline and for 14 days after letermovir initiation. Descriptive statistics were used for baseline characteristics and select outcomes. Wilcoxon Sign Rank test was utilized for the primary outcome comparing C/D pre- and post- letermovir initiation. <h3>Results</h3> Patient characteristics are described in Table 1. The median C/D of all immunosuppressive agents were not significantly different after letermovir initiation (Table 2). Median time to resolution of leukopenia/neutropenia was 6 days and time to CMV viremia clearance in those treated was 45 days. <h3>Conclusion</h3> In this cohort of LTRs switched to letermovir for CMV prophylaxis or treatment, immunosuppression C/D ratios were not significantly different after conversion. Empiric dose adjustment is likely unnecessary for all LTRs; future studies should clarify the optimal use of letermovir in the SOT population.