Mortality in recipients of allogeneic haematopoietic cell transplantation in the era of cytomegalovirus primary prophylaxis: a single-centre retrospective experience

Objectives: Allogeneic haematopoietic cell transplant (allo-HCT) recipients who are cytomegalovirus (CMV)-seronegative have better post-transplant outcomes than CMV-seropositive recipients. Letermovir (LTV) is approved for CMV primary prophylaxis in adults who are CMV-seropositive after allo-HCT, and its use is associated with improved long-term post-transplant outcomes. We analysed whether LTV has affected the relationship between CMV serostatus and post-transplant outcomes. Methods: We conducted a retrospective single-centre cohort study of allo-HCT recipients, stratified according to donor (D) and recipient (R). CMV serostatus and the use of LTV: D⁻/R⁻, R⁺/LTV⁻, and R⁺/LTV⁺. Outcomes measured were all-cause and non-relapse mortality, clinically significant CMV infection, graft-versus-host disease, and relapse up to week 48 after allo-HCT. The D⁻/R⁻ group served as the reference for comparisons in univariate, competing risk regression, and cumulative incidence functions. Results: The analysis included 1071 consecutive allo-HCT recipients: 131 D⁻/R⁻, 557 R+/LTV⁻, and 383 R+/LTV+. All-cause mortality by day 100 was 6.1% for the D⁻/R⁻ group, compared with 14.0% (p 0.024) and 7.8% (p 0.7) for the R+/LTV⁻ and R+/LTV + groups, respectively. Non-relapse mortality by day 100 was 11.0%, 6.8% and 3.8% for R+/LTV⁻, R+/LTV+, and D⁻/R⁻ groups, respectively, without significant difference. When including relapse as a competing event, the hazard ratio for non-relapse mortality was 1.83 (95% CI: 1.12–2.99, p 0.017) for R+/LTV⁻ compared with D⁻/R⁻ and 1.05 (95% CI 0.62–1.77, p 0.85) for R+/LTV + compared with D⁻/R⁻. Discussion: CMV primary prophylaxis with LTV abrogated the mortality gap based on CMV serostatus, a protective effect that persisted after discontinuation of primary prophylaxis.