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

Per Ljungman, Michael Schmitt, Francisco M Marty, Johan Maertens, Roy F Chemaly, Nicholas A Kartsonis, Joan R Butterton, Hong Wan, Valerie L Teal, Kendra Sarratt, Yoshihiko Murata, Randi Y Leavitt, Cyrus Badshah, Per Ljungman, Michael Schmitt, Francisco M Marty, Johan Maertens, Roy F Chemaly, Nicholas A Kartsonis, Joan R Butterton, Hong Wan, Valerie L Teal, Kendra Sarratt, Yoshihiko Murata, Randi Y Leavitt, Cyrus Badshah

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.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

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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