Clinical "Real-World" Experience with Letermovir for Prevention of Cytomegalovirus Infection in Allogeneic Hematopoietic Cell Transplant Recipients

Abstract

<h3>Introduction</h3> Cytomegalovirus (CMV) is the most common opportunistic infection following hematopoietic cell transplantation (HCT). Letermovir was approved in 2017 by the Food and Drug Administration (FDA) for prevention of CMV infection in allogeneic HCT patients. Letermovir was shown to be safe and effective in the phase 3 trial but published post-marketing data with this new agent is scarce. <h3>Objectives</h3> To describe our "real-world" clinical experience with letermovir. <h3>Methods</h3> Twenty-five CMV positive (R+) allogeneic HCT recipients transplanted between March 2018 and January 2019 who received letermovir prophylaxis (until day 100) were included in the treatment group. A historical group of 106 CMV R+ allogeneic HCT recipients transplanted between September 2012 and June 2016 who underwent CMV preemptive therapy served as control group. We compared the incidence of both CMV reactivation (any viremia) and clinically significant CMV infection (CS-CMVi; defined as any detectable CMV DNAemia leading to preemptive treatment or presence of CMV tissue invasive disease) between initiation of letermovir and days +100 and +200 post-HCT. <h3>Results</h3> CMV reactivation within 100 days post-HCT was lower in the letermovir group vs. control group (20% vs. 72% respectively, P<0.001) [Figure 1]. The 100-day cumulative incidence of CS-CMVi was significantly lower in the letermovir group vs. control group (4% vs. 59% respectively, P<0.001) [Figure 2] with no tissue invasive disease in the former. Significantly reduced incidence of CMV reactivation and CS-CMVi were also observed at 200 days in the letermovir group. No difference in mortality was observed between the two groups (20% vs. 21% respectively, P 0.79) in the first 100 days post-HCT. <h3>Conclusion</h3> This study confirms the efficacy of letermovir in preventing CMV reactivation in CMV R+ allogeneic HCT recipients in first 100 days post-HCT and suggests sustained efficacy after discontinuation of prophylaxis. Further studies are needed to investigate the role of letermovir use beyond 100 days post-HCT.