A Mortality Analysis of Letermovir Prophylaxis for Cytomegalovirus (CMV) in CMV-seropositive Recipients of Allogeneic Hematopoietic Cell Transplantation.

Autor:	Ljungman P; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden., Schmitt M; University of Heidelberg, Germany., Marty FM; Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts., Maertens J; Universitaire Ziekenhuizen Leuven, Belgium., Chemaly RF; University of Texas, MD Anderson Cancer Center, Houston., Kartsonis NA; Merck & Co., Inc., Kenilworth, New Jersey., Butterton JR; Merck & Co., Inc., Kenilworth, New Jersey., Wan H; Merck & Co., Inc., Kenilworth, New Jersey., Teal VL; Merck & Co., Inc., Kenilworth, New Jersey., Sarratt K; Merck & Co., Inc., Kenilworth, New Jersey., Murata Y; Merck & Co., Inc., Kenilworth, New Jersey., Leavitt RY; Merck & Co., Inc., Kenilworth, New Jersey., Badshah C; Merck & Co., Inc., Kenilworth, New Jersey.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2020 Apr 10; Vol. 70 (8), pp. 1525-1533.
DOI:	10.1093/cid/ciz490
Abstrakt:	Background: In a phase 3 trial, letermovir reduced clinically significant cytomegalovirus infections (CS-CMVi) and all-cause mortality at week 24 versus placebo in CMV-seropositive allogeneic hematopoietic cell transplantation (HCT) recipients. This post hoc analysis of phase 3 data further investigated the effects of letermovir on all-cause mortality. Methods: Kaplan-Meier survival curves were generated by treatment group for all-cause mortality. Observations were censored at trial discontinuation for reasons other than death or at trial completion. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox modeling, adjusting for risk factors associated with mortality. Results: Of 495 patients with no detectable CMV DNA at randomization, 437 had vital-status data available through week 48 post-HCT at trial completion (101 deaths, 20.4%). Following letermovir prophylaxis, the HR for all-cause mortality was 0.58 (95% CI, 0.35-0.98; P = .04) at week 24 and 0.74 (95% CI, 0.49-1.11; P = .14) at week 48 post-HCT versus placebo. Incidence of all-cause mortality through week 48 post-HCT in the letermovir group was similar in patients with or without CS-CMVi (15.8 vs 19.4%; P = .71). However, in the placebo group, all-cause mortality at week 48 post-HCT was higher in patients with versus those without CS-CMVi (31.0% vs 18.2%; P = .02). The HR for all-cause mortality in patients with CS-CMVi was 0.45 (95% CI, 0.21-1.00; P = .05) at week 48 for letermovir versus placebo. Conclusions: Letermovir may reduce mortality by preventing or delaying CS-CMVi in HCT recipients. Clinical Trials Registration: clinicaltrials.gov, NCT02137772. (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)
Databáze:	MEDLINE
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