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

At 1 year after hematopoietic cell transplant (HCT), letermovir prophylaxis (LET) was associated with closing the mortality disparity between cytomegalovirus 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. 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.