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Clin Infect Dis. 2019 Jun 8. pii: ciz490. doi: 10.1093/cid/ciz490. [Epub ahead of print]

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

Author information

1
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
2
University of Heidelberg, Heidelberg, Germany.
3
Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA, USA.
4
Universitaire Ziekenhuizen Leuven, Leuven, Belgium.
5
University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
6
Merck & Co., Inc., Kenilworth, NJ, USA.

Abstract

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 (ClinicalTrials.gov, NCT02137772). This post-hoc analysis of Phase 3 data investigated the effects of letermovir on all-cause mortality further.

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.

KEYWORDS:

cytomegalovirus; hematopoietic-cell transplantation; letermovir; mortality

PMID:
31179485
DOI:
10.1093/cid/ciz490

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