Letermovir Prophylaxis for CMV Reactivation in Allogeneic Stem Cell Recipients: A Retrospective Single Center Analysis

Abstract

Background/Aim: Cytomegalovirus (CMV) reactivation is one of the most clinically significant complications in allogeneic stem cell recipients and a frequent cause for transplantation related mortality. Letermovir is a newly available and recently approved drug for CMV prophylaxis. In a retrospective single center analysis, we investigated the benefit of letermovir as CMV prophylaxis in allogeneic stem cell recipients. Patients and Methods: We included 48 CMV-seropositive transplant recipients from January 2017 to August 2020 from our department. We compared the rate of CMV reactivation in patients who received letermovir as prophylaxis from day 0 after allogeneic stem cell transplantation (alloSCT) with a control group that did not receive CMV prophylaxis. The primary endpoint was CMV reactivation and was defined as an increase of CMV copies over 1250 Ul/ml in the peripheral blood; secondary endpoints were overall survival (OS) up to 180 days, engraftment and all-cause mortality. Results: We included 21 patients in the control group and 27 patients in the letermovir group. Letermovir treatment led to a significantly reduced incidence of CMV reactivation after alloSCT (33.3% in the letermovir group versus 76.2% in the control group, p<0.001). The OS at day 180 was 80.9% in the control group versus 92.6% in the letermovir group (p<0.05). The median duration of letermovir prophylaxis was 192±104 days. Conclusion: Our results indicate that letermovir prophylaxis is associated with a significant lower risk of CMV reactivation and improved overall survival in CMV-seropositive stem cell recipients. Moreover, a prolonged use of letermovir prophylaxis might be a survival benefit.

Immunovirology of cytomegalovirus infection in allogeneic stem cell transplant recipients undergoing prophylaxis with letermovir: A narrative review

“…There is solid evidence for the clinical efficacy of primary prophylaxis (also secondary) with LMV in preventing csCMV‐I and CMV end‐organ disease in adult CMV seropositive allo‐SCT patients and, to a much lesser extent, in pediatric patients, both in randomized trials and in a real‐life setting 13,48–81 . A comprehensive review and meta‐analysis on this subject was recently published 14 .…”

A new direction for cytomegalovirus prophylaxis among transplant recipients: Benefits and nonviral outcomes of letermovir use as primary CMV prophylaxis

“…Given prior evidence that demonstrates increased risk of clinically significant-CMV infection occurrence following discontinuation of primary prophylaxis, the ability to extend letermovir durations out to 200 days following transplant may allow for enhanced protection during periods of more intense immunosuppression [12 ▪▪ ,22,23]. Additionally, this favorable safety profile allows for less concern related to initiation timing of primary prophylaxis among HSCT recipients due to limited association with bone marrow suppression and delayed engraftment [10,24].…”

“…22,23]. Additionally, this favorable safety profile allows for less concern related to initiation timing of primary prophylaxis among HSCT recipients due to limited association with bone marrow suppression and delayed engraftment [10,24].…”