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

• Published in: Clinical infectious diseases Vol. 70; no. 8; pp. 1525 - 1533
• Main Authors: Ljungman, Per, Schmitt, Michael, Marty, Francisco M, Maertens, Johan, Chemaly, Roy F, Kartsonis, Nicholas A, Butterton, Joan R, Wan, Hong, Teal, Valerie L, Sarratt, Kendra, Murata, Yoshihiko, Leavitt, Randi Y, Badshah, Cyrus
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 10.04.2020
• Subjects: Acetates; and Commentaries; Antiviral Agents - therapeutic use; Cytomegalovirus; Cytomegalovirus Infections - drug therapy; Cytomegalovirus Infections - prevention & control; Hematopoietic Stem Cell Transplantation; Humans; Medicin och hälsovetenskap; Quinazolines; letermovir; mortality; cytomegalovirus; hematopoietic cell transplantation
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/ciz490

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. This post hoc mortality analysis of phase 3 data suggests that letermovir prophylaxis reduced all-cause mortality versus placebo in cytomegalovirus (CMV)-seropositive allogeneic hematopoietic-cell transplantation recipients by preventing or delaying clinically significant CMV infections.