Real‐world Efficacy of Extending Duration of Letermovir Prophylaxis for Allogeneic Stem Cell Recipients

ABSTRACT Background Cytomegalovirus (CMV) reactivation following allogeneic hematopoietic stem cell transplantation (HSCT) leads to significant morbidity and mortality. Recently, a pivotal trial demonstrated extended duration of letermovir until post‐HSCT Day 200 reduced clinically significant CMV infection (csCMVi). Here we evaluated the real‐world efficacy of extended letermovir. Methods We retrospectively reviewed consecutive patients who underwent HSCT and received letermovir prophylaxis for CMV seropositivity of the donor and/or the recipient at a transplant center between July 2018 and March 2024. Results A total of 236 HSCTs with letermovir prophylaxis were performed. Letermovir was administered until Days 75–125 in 189 cases, and until Day 150‐ in 37 cases, who were assigned as short and extended letermovir group, respectively. The cumulative incidence of csCMVi at Day 200 was significantly lower in cases with extended letermovir, with no patient developed csCMVi in this group compared to 26.8% in short prophylaxis group ( p < 0.001). However, the incidence was comparable at Day 400, with 19.7% in extended and 28.4% in short prophylaxis group ( p = 0.14). Multivariable analysis for csCMVi showed age ≥ 50 years at HSCT (hazard ratio [HR], 3.24; p < 0.001) and steroid administration at letermovir discontinuation (HR, 2.25; p = 0.003) were identified as significant risk factors, and patients with both factors were associated with higher incidence of csCMVi regardless of letermovir duration. Immunoglobulin G, but not lymphocyte count, was persistently lower in these high‐risk patients until Day 400. Conclusion Despite the efficacy of letermovir in preventing csCMVi during immunosuppression, the occurrence of csCMVi following letermovir cessation was still a clinical concern. image