Impact of Letermovir Use for Cytomegalovirus Prophylaxis on Re-Hospitalization Following Allogeneic Hematopoietic Stem Cell Transplantation: An Analysis of a Phase III Randomized Clinical Trial

Abstract

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with substantial healthcare resource use, particularly when recipients develop cytomegalovirus (CMV) infection. Letermovir reduced post-HSCT CMV infection risk compared with placebo in a previous phase III trial. This analysis evaluated letermovir’s impact on re-hospitalization post-transplant. Methods: Using data from a phase III, multicenter, randomized clinical trial (NCT02137772, registered May 14, 2014), this study assessed CMV-associated and all-cause re-hospitalizations at weeks 14, 24, and 48 post-transplant among recipients of letermovir versus placebo. Unstandardized re-hospitalization rates and days were reported; standardized rates and days were estimated accounting for censoring due to death or early study discontinuation. Results: Unstandardized rates (95% confidence interval [CI]) of all-cause re-hospitalization in letermovir versus placebo recipients at weeks 14, 24, and 48 were 36.6% (31.4–42.1) versus 47.6% (39.9–55.4), 49.2% (43.7–54.8) versus 55.9% (48.1–63.5), and 55.7% (50.1–61.2) versus 60.6% (52.8–68.0), respectively. Unstandardized mean total duration (95% CI) of re-hospitalization with letermovir versus placebo at weeks 14, 24, and 48 were 7.6 (5.9–9.8) versus 11.3 (8.6–14.8), 13.9 (11.2–17.2) versus 15.5 (11.9–20.1), and 18.0 (14.8–21.9) versus 20.7 (15.8–27.1) days, respectively. Similar results were found in CMV-associated re-hospitalization outcomes and standardized rates and days of all-cause re-hospitalizations. Conclusions: In this post-hoc analysis, letermovir was associated with lower rates of CMV-associated and all-cause re-hospitalizations with a shorter length of stay (especially within the first 14 weeks post-transplant).