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Clinical Trial
. 2020 Apr 10;70(8):1525-1533.
doi: 10.1093/cid/ciz490.

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

Per Ljungman  1 , Michael Schmitt  2 , Francisco M Marty  3 , Johan Maertens  4 , Roy F Chemaly  5 , Nicholas A Kartsonis  6 , Joan R Butterton  6 , Hong Wan  6 , Valerie L Teal  6 , Kendra Sarratt  6 , Yoshihiko Murata  6 , Randi Y Leavitt  6 , Cyrus Badshah  6
Affiliations
Clinical Trial

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

Per Ljungman et al. Clin Infect Dis. .

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. 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.

Keywords: cytomegalovirus; hematopoietic cell transplantation; letermovir; mortality.

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Figures

Figure 1.
Figure 1.
All-cause mortality through week 48 post-HCT in participants with (A) and without (B) CS-CMVi through week 24 post-HCT. Abbreviations: CI, confidence interval; CS-CMVi, clinically significant cytomegalovirus infection; HCT, hematopoietic stem-cell transplantation; KM, Kaplan-Meier.
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References

    1. Boeckh M, Ljungman P. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood 2009; 113:5711–9. - PMC - PubMed
    1. Ljungman P, Hakki M, Boeckh M. Cytomegalovirus in hematopoietic stem cell transplant recipients. Hematol Oncol Clin North Am 2011; 25:151–69. - PMC - PubMed
    1. Green ML, Leisenring W, Stachel D, et al. . Efficacy of a viral load-based, risk-adapted, preemptive treatment strategy for prevention of cytomegalovirus disease after hematopoietic cell transplantation. Biol Blood Marrow Transplant 2012; 18:1687–99. - PMC - PubMed
    1. Schmidt-Hieber M, Labopin M, Beelen D, et al. . CMV serostatus still has an important prognostic impact in de novo acute leukemia patients after allogeneic stem cell transplantation: a report from the Acute Leukemia Working Party of EBMT. Blood 2013; 122:3359–64. - PubMed
    1. Boeckh M, Leisenring W, Riddell SR, et al. . Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. Blood 2003; 101:407–14. - PubMed

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