Impact of Letermovir Primary Cytomegalovirus Prophylaxis on 1-Year Mortality After Allogeneic Hematopoietic Cell Transplantation: A Retrospective Cohort Study

Abstract

Abstract Background Cytomegalovirus (CMV)–seropositive (R+) hematopoietic cell transplant (HCT) recipients have a survival disparity compared with CMV-seronegative recipient/donor (R–D–) pairs. We hypothesized that primary letermovir prophylaxis (LET) may abrogate this disparity. We investigated the relationship between LET and mortality at 1 year post-HCT. Methods In this retrospective cohort study, we included adult R–D– or R+ patients who received HCT pre-LET (between 1 January 2013 through 15 December 2017) and post-LET (between 16 December 2017 through December 2019). R+ were categorized by LET receipt as R+/LET or R+/no-LET. Cox proportional hazard models were used to estimate the association of LET with all-cause mortality at 1 year after transplantation. Results Of 848 patients analyzed, 305 were R–D–, 364 R+/no-LET, and 160 R+/LET. Because of similar mortality (adjusted hazard ratio [aHR], 1.29 [95% confidence interval {CI}, .76–2.18]; P = .353]) between pre-LET/R–D– and post-LET/R–D–, R–D– were combined into 1 group. Compared with R–D–, the aHR for mortality was 1.40 (95% CI, 1.01–1.93) for R+/no-LET and 0.89 (95% CI, .57–1.41) for R+/LET. Among R+, LET was associated with decreased risk of death (aHR, 0.62 [95% CI, .40–.98]); when conventional HCT and T-cell depleted HCT were analyzed separately, the aHR was 0.86 (95% CI, .51–1.43) and 0.21 (95% CI, .07–.65), respectively. Conclusions At 1 year post-HCT, LET was associated with closing the mortality disparity between R–D– and R+. Among all R+, LET was associated with decreased mortality, driven by 79% reduced incidence of death in T-cell depleted HCT.