Mortality in recipients of allogeneic hematopoietic cell transplantation in the era of cytomegalovirus primary prophylaxis: A single center retrospective Experience

Objectives Allogeneic hematopoietic 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 analyzed whether LTV has affected the relationship between CMV serostatus and post-transplant outcomes. Methods We conducted a retrospective single-center 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 to 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= .017) for R+/LTV- compared to D-/R-, and 1.05 (95% CI 0.62-1.77, P= .85) for R+/LTV+ compared to D-/R-. Conclusions CMV primary prophylaxis with LTV abrogated the mortality gap based on CMV serostatus, a protective effect that persisted after discontinuation of primary prophylaxis.