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

Abstract

Background 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 1year post-HCT. Methods In this retrospective cohort study, we included adult R-D- or R+ patients who received HCT pre-LET (between January 1, 2013 through December 15, 2017) and post-LET (between December 16, 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 one-year post-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] [95% confidence interval]); 1.29 [0.76-2.18; p=0.353] between pre-LET/R-D- and post-LET/R-D-, R-D- were combined into one group. Compared with R-D-, the aHR for mortality was 1.40 [1.01-1.93] for R+/no-LET and 0.89 [0.57-1.41] for R+/LET. Among R+, LET was associated with decreased risk of death (aHR 0.62 [0.40-0.98]); when conventional and T-cell depleted HCT were analyzed separately, the aHR was 0.86 [0.51-1.43] and 0.21 [0.07-0.65] respectively. Conclusions At one-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.

New trends in the management of cytomegalovirus infection after allogeneic hematopoietic cell transplantation: a survey of the Infectious Diseases Working Pary of EBMT

“…In this regard, our interpretation of existing data support that a broader use of letermovir primary prophylaxis in the next future may result into an improvement of the overall transplant outcomes, as suggested by a post-hoc analysis on overall mortality conducted on the patients recruited in the phase III trial of letermovir versus placebo [24]. Moreover, a retrospective single-centre study comparing the outcome of two adult cohorts of patients, transplanted before and after the introduction of letermovir prophylaxis, respectively, showed that the 1-year mortality of letermovir-treated cohort was significantly reduced compared with that of no-letermovir-treated cohort and superimposable to that of CMV negative recipient/donor pairs [25].…”

Extended-duration letermovir prophylaxis for cytomegalovirus infection after cord blood transplantation in adults

“…The efficacy of letermovir prophylaxis in reducing the risk of csCMVi after HSCT is well established. 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 27 However, high rates of late csCMVi have been observed when letermovir prophylaxis is limited to the first 100 days’ posttransplant, especially in high-risk patient groups such as HLA-disparate donor recipients. 11 , 22 A single-center analysis has shown that extending prophylaxis duration beyond 100 days is highly effective in preventing csCMVi in patients with GVHD, another high-risk patient group.…”

New trends in the management of cytomegalovirus infection after allogeneic hematopoietic cell transplantation: a survey of the Infectious Diseases Working Party of EBMT

“…In this regard, our interpretation of existing data support that a broader use of letermovir primary prophylaxis in the next future may result into an improvement of the overall transplant outcomes, as suggested by a post-hoc analysis on overall mortality conducted on the patient recruited in the phase III trial of letermovir versus placebo 24 . Moreover, a retrospective single-centre study comparing the outcome of two adult cohorts of patients, transplanted before and after the introduction of letermovir prophylaxis, respectively, showed that the 1-year mortality of letermovir-treated cohort was signi cantly reduced compared with that of noletermovir-treated cohort and superimposable to that of CMV negative recipient/donor pairs 25 .…”