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

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.
Competing Interests: Potential conflicts of interest. S. G. has received research funding from Miltenyi Biotec, Takeda, Celgene, Amgen, Sanofi, Johnson & Johnson, and Actinium Pharmaceuticals, and is on the advisory boards for Kite Pharmaceuticals, Celgene, Sanofi, Novartis, Johnson & Johnson, Amgen, Takeda, Jazz Pharmaceuticals, and Actinium Pharmaceuticals. M.-A. P. has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, and Novartis; has received honoraria from AbbVie, Bellicum, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Celgene, Equilium, Karyopharm, Kite/Gilead, Miltenyi Biotec, MorphoSys, Omeros, OrcaBio, VectivBio AG, Vor Biopharma, and Takeda; has served on data and safety monitoring boards for Servier, Cidara Therapeutics, Sallas Life Sciences, and Medigene and scientific advisory boards for MolMed and NexImmune; and holds ownership interests in NexImmune and Omeros. G. P. has served as an investigator for Merck & Co and Shire/Takeda; has received research grant support from Merck & Co; has received consulting and other fees from Chimerix, Astellas, Merck, Cidara, Amplyx, AlloVir, Takeda/Shire, Behring, Octapharma, SymBio, Shionogi, Partners Therapeutics, ADMA Biologics, Vera, and Siemens Healthineers; has received payment and honoraria for continuing medical education programs from PeerView, PeerVoice, Vindico, and Medscape; has received speaker’s fees from Merck & Co; and has served as a data safety and monitoring committee (DSMC) member for Amplyx and Vera, DCSM chair for AlloVir, Endpoint Adjudication Committee (EAC) Chair for Octapharma, and advisory board member for ADMA Biologics, Astellas Pharma, Cidara, Octapharma, Partners Therapeutics, Shionogi, Behring, Takeda, and Siemens Healthineers. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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