Real-World Utilization Pattern and Outcomes of Letermovir in Adult Cytomegalovirus-Seropositive Allogeneic Hematopoietic Cell Transplant Recipients: An International Retrospective Study From the Infectious Diseases Working Party of EBMT.

INTRODUCTION The objective of this study was to analyze outcomes associated with letermovir for CMV primary prophylaxis in adult CMV-seropositive allo-HCT recipients in a multicenter real-world scenario.

METHODS This retrospective real-world international study involved 481 adults undergoing allo-HCT between 2018 and 2020 who received letermovir for primary prophylaxis. Outcomes included clinically significant CMV infection (csCMVi), graft-versus-host disease, opportunistic infections, all-cause mortality, hospitalizations, and ICU admissions. The median follow-up was 33.8 months.

RESULTS The median start time of letermovir was 3 days after transplant, with a median duration of prophylaxis of 100 days. The cumulative incidence of csCMVi was 2.7% (95% CI = 1.5-4.5) at 3 months, 13.1% (95% CI = 10.3-16.3) at 6 months, and 17.1% (95% CI = 13.9-20.6) at 12 months. The median time from HCT to csCMVi was 142 days. In multivariate analysis, four factors contributed to development of csCMVi: reduced-intensity conditioning (HR = 1.90; 95% CI = 1.17-3.08; p = 0.009), peripheral blood as cell source (HR = 2.92; 95% CI = 1.00-8.50; p = 0.0495), pretransplant CMV serostatus D-/R+ (HR = 2.24; 95% CI = 1.42-3.53; p = 0.0005), use of alemtuzumab (HR = 3.91; 95% CI = 1.60-9.59; p = 0.003). There was no difference in the cumulative incidence of csCMVi in the first 100 days between patients who started letermovir ≤ 5 versus > 5 days after transplant. Factors adversely contributing to overall survival: age as a continuous variable, 10-year effect (HR = 1.23; 95% CI = 1.08-1.41; p = 0.002), patient male sex (HR = 1.48; 95% CI = 1.02-2.13; p = 0.038), status > CR1 of disease at transplant (HR = 1.97; 95% CI = 1.36-2.85; p = 0.0004), PB as stem cell source (HR = 1.81; 95% CI = 1.04-3.15; p = 0.04), acute leukemia diagnosis (HR = 1.61; 95% CI = 1.10-2.34; p = 0.01), CMV high-risk patients (HR = 1.52; 95% CI = 1.02-2.27; p = 0.04).

CONCLUSIONS An analysis of real-world use of letermovir in CMV prophylaxis after allo-HCT showed a low incidence of csCMVi compared to previously published information.