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

Summary 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.