Use of Letermovir for Cytomegalovirus (CMV) Prophylaxis in Orthotopic Heart Transplant Recipients

Abstract

<h3>Purpose</h3> Valganciclovir is typically used for post-transplant CMV prophylaxis. Many patients have difficulty tolerating valganciclovir due to adverse events including leukopenia which limit its use. This problem is exacerbated by concomitant use of other agents that promote leukopenia in post-transplant recipients such as mycophenolate mofetil and trimethoprim-sulfamethoxazole. Letermovir has been approved for CMV prophylaxis in adult hematopoietic stem cell transplant patients, however there is a paucity of data on the use of letermovir in heart transplant (HT) recipients. This study aims to evaluate the efficacy and safety of letermovir in HT patients. <h3>Methods</h3> In this retrospective chart review, we examined the usage of letermovir post-HT at a large academic medical center. All patients treated with letermovir in a period between November 2019 and October 2021 (24 months) were enrolled in this analysis. <h3>Results</h3> Thirteen patients were started on letermovir. The mean age was 55.9±13 years, 46% of the patients were male, and 85.7% had a non-ischemic cardiomyopathy. Most common comorbidities were chronic kidney disease (53.8%) and hypertension (46.2%). 85.8% of patients had a high-risk mismatch (CMV D+/R-) and 14.2% had a moderate-risk mismatch (7.1% D-/R+, 7.1% D+/R+). For all patients the indication for letermovir was leukopenia. The average nadir WBC was 1.9±0.7 on valganciclovir. 61.5% (8 of 13) of patients required granulocyte colony-stimulating factor while on valganciclovir. All 13 patients (100%) had their mycophenolate dose held or adjusted while on valganciclovir and 38.4% (5 of 13) had their mycophenolate discontinued permanently while on valganciclovir. Patients were on letermovir for an average of 4.1±4.7 months. 23.1% (3/13) patients had breakthrough viremia, one in the setting of non-adherence. One patient had to discontinue letermovir due to side effects (headache, body aches). At the end of the study period, 11/13 patients were on letermovir. All 13 patients had their tacrolimus dosages decreased once switched to letermovir. 1 patient required hospitalization due to symptomatic tacrolimus toxicity. <h3>Conclusion</h3> For HT recipients who cannot tolerate valganciclovir, letermovir presents an alternative for CMV prophylaxis; however, close monitoring for breakthrough CMV and CNI level elevation is necessary. Further larger studies are required.