Clinical “real‐world” experience with letermovir for prevention of cytomegalovirus infection in allogeneic hematopoietic cell transplant recipients

Abstract

BackgroundLetermovir was approved in 2017 for prevention of cytomegalovirus (CMV) infection in seropositive (R+) allogeneic hematopoietic cell transplantation (HCT) patients. Post‐marketing data with this new agent are scarce.MethodsWe compared the incidence of both CMV reactivation (any viremia) and clinically significant CMV infection (CS‐CMVi; CMV DNAemia leading to preemptive treatment or presence of CMV tissue invasive disease) at days +100 and +200 post‐HCT in 25 adult allogeneic HCT patients who received letermovir prophylaxis (until day 100) and a historical control group of 106 CMV R+ allogeneic HCT recipients who underwent CMV preemptive therapy.ResultsCMV reactivation within 100 days post‐HCT was lower in the letermovir group vs control group (20% vs 72% respectively, P < .001). The 100‐day cumulative incidence of CS‐CMVi was significantly lower in the letermovir group vs control group (4% vs 59% respectively, P < .001). Significantly reduced incidence of CMV reactivation and CS‐CMVi was also observed at 200 days in the letermovir group. No difference in mortality was observed between the two groups.ConclusionThis 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.

Letermovir Prophylaxis and Cytomegalovirus Reactivation in Adult Hematopoietic Cell Transplant Recipients with and without Acute Graft Versus Host Disease

“…Anderson and colleagues conducted a retrospective analysis of 25 patients who received letermovir and 106 patients who did not that assessed the use of letermovir outside of a clinical trial setting. They reported that the cumulative incidence of CS-CMVi at 100 days post-allo-HCT was only 4% in patients who received letermovir compared to 59% who did not receive letermovir [ 14 ]. Studer and colleagues also published a retrospective analysis similar to Anderson and colleagues, but with a larger patient population of 432 patients [ 16 ].…”

“…Letermovir is an oral antiviral agent that inhibits the CMV-terminase complex to prevent CMV replication. Letermovir’s novel mechanism has no cross-resistance with other antiviral agents and has a favorable side effect profile, which makes it ideal for use in the prophylactic setting [ 13 , 14 ]. In controlled and retrospective trials, letermovir prophylaxis has demonstrated reduction in the incidence of CMV infection [ 15 ].…”

“…In a mortality analysis of the same phase 3 trial, among patients who developed CS-CMVi, the mortality rate was lower in patients who received letermovir (15.8%) compared to placebo (31%) [ 6 ]. Two retrospective studies also demonstrated reduced CS-CMVi or CMV viremia in patients who received letermovir compared to a control group [ 14 , 16 ]. While these studies included patients with GVHD, they were limited by a relatively small sample size and only a small portion of patients had received letermovir [ 14 , 15 , 16 ].…”

“…Two retrospective studies also demonstrated reduced CS-CMVi or CMV viremia in patients who received letermovir compared to a control group [ 14 , 16 ]. While these studies included patients with GVHD, they were limited by a relatively small sample size and only a small portion of patients had received letermovir [ 14 , 15 , 16 ]. One small retrospective study found that extended letermovir administration beyond day 100 post allo-HCT is effective for CMV prophylaxis in patients with GVHD who require systemic immunosuppression, and that the presence of acute GVHD (aGVHD) grade ≥ 2 was associated with increased all-cause mortality [ 17 ].…”

BSHI guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

“…In cases where a suitable CMV-matched donor cannot be identified, Letermovir offers a prohylactic treatment to reduce the risk of CMV reactivation for seropositive patients receiving a seronegative donation. As knowledge of the impact of letermovir in HPCT increases and more randomized clinical trials are conducted, its best use in CMV management will be further realized (Anderson et al, 2020;El Helou & Razonable, 2019).…”