Tolerability and clinical efficacy of letermovir for primary cytomegalovirus prophylaxis after heart transplantation

Abstract

Background: Letermovir (LET) is a newer antiviral that has successfully been used for primary cytomegalovirus (CMV) prophylaxis in kidney transplant recipients. Valganciclovir (VGC), the current first-line CMV antiviral, is effective at prophylaxis but carries a significant risk of myelotoxicity with related downstream consequences. We studied the tolerability and clinical effectiveness of LET for primary CMV prophylaxis after heart transplant (HT) and compared rates of neutropenia and CMV disease to a historical HT cohort.

Methods: All single-organ, first-time HTs at our center who gave informed consent and were eligible to receive primary CMV prophylaxis (not CMV donor/recipient seronegative) were included. Subjects were subsequently excluded if they needed renal replacement therapy or did not survive >72 hours post-HT. Outcomes were compared to a historical control group (N = 204) treated with VGC for CMV prophylaxis.

Results: Thirty-two patients completed 3 or 6 months of LET prophylaxis. There were no episodes of neutropenia while on LET compared to 15% (30/204) in the historical VGC group (p = 0.02). There were no breakthrough CMV deoxyribonucleic acid (DNA) infections compared to 3% (5/204) in the VGC group (p = 0.37). No patients stopped LET early due to adverse effects.

Conclusions: LET is well tolerated and shows comparable clinical effectiveness for primary CMV prophylaxis post-HT compared to a historical, predominantly VGC prophylaxis cohort. LET prophylaxis was associated with no cases of neutropenia nor breakthrough CMV DNAemia in this prospective cohort. Study of the cost-effectiveness of LET for primary CMV prophylaxis post-HT is warranted.

Keywords: CMV; heart transplant; letermovir; leukopenia; primary prophylaxis.