A real-world study on different initiation times and treatment durations of letermovir for cytomegalovirus prophylaxis after allogeneic haematopoietic stem cell transplantation.

Cytomegalovirus (CMV) reactivation is a frequent complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT), but the timing and duration of letermovir prophylaxis in routine practice remain uncertain. We retrospectively reviewed 97 allo-HSCT recipients who received letermovir as primary prophylaxis, focusing on CMV-related outcomes, transplant complications, survival and safety. Letermovir was initiated on day 0 in 31 patients, on day +7 in 44 patients, and on day +14 in 22 patients. The cohort was also stratified by prophylaxis duration, with 51 patients receiving 100-day prophylaxis and 46 patients receiving 200-day prophylaxis. Earlier initiation was associated with a lower 100-day cumulative incidence (CIR) of CMV DNAemia/csCMVi (6.5% vs. 18.2% vs. 36.4%; Gray's test p = 0.008), later first CMV deoxyribonucleic acid (DNA) detection (median 78 vs. 54 vs. 36 days; p = 0.005) and a shorter duration of DNAemia. Compared with the 200-day group, the 100-day group had more late CMV reactivation after discontinuation during follow-up (21.6% vs. 0%; p < 0.001) and numerically lower 1-year overall survival (80.4% [95% confidence interval (CI), 66.6-88.9] vs. 93.5% [95% CI, 81.1-97.8]; log-rank p = 0.103), without more severe chronic graft-versus-host disease or grade ≥3 drug-related adverse events. These real-world findings suggest that both earlier initiation and longer letermovir prophylaxis deserve further evaluation after allo-HSCT.