Differential Clinical Impact of Letermovir Prophylaxis According to Graft Sources: a KSGCT Multicenter Retrospective Analysis.

Clinically significant cytomegalovirus infection (csCMVi) is frequently observed after allogeneic hematopoietic stem cell transplantation (HSCT) and prophylaxis with letermovir is commonly adopted. However, the clinical benefit of letermovir prophylaxis according to graft sources has not been sufficiently elucidated. We retrospectively analyzed 2,194 CMV-seropositive HSCT recipients (236 with letermovir prophylaxis and 1,958 without prophylaxis against CMV). csCMVi was significantly less frequent in patients with than in those without letermovir prophylaxis (23.7% vs 58.7% at 100 days after HSCT, p<0.001) and the same tendency was seen when bone marrow (BM), peripheral blood stem cell (PBSC) and cord blood (CB) transplantation recipients were separately analyzed. In BM recipients, non-relapse mortality (NRM) was significantly lower in the letermovir group at 6 months post-HSCT (5.0% vs 14.9%, p=0.018), and the same tendency was observed in PBSC recipients (14.7% vs 24.8%, p=0.062) ; however, there was no statistical significance at 1 year (BM, 21.1% vs 30.4%, p=0.67; PBSC, 21.2% vs 30.4%, p=0.096). In contrast, NRM was comparable between CB recipients with and without letermovir prophylaxis throughout the clinical course (6 months, 23.6% vs 24.3%, p=0.92; 1 year, 29.3% vs 31.0%, p=0.77, which was confirmed by multivariate analyses. In conclusion, the impact of letermovir prophylaxis on NRM and csCMVi should be separately considered according to graft sources.