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.
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
Russo, DomenicoMembro del Collaboration Group
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2026-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
