Letermovir prophylaxis is effective in preventing cytomegalovirus reactivation after allogeneic hematopoietic cell trans
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ORIGINAL ARTICLE
Letermovir prophylaxis is effective in preventing cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation: single-center real-world data Patrick Derigs 1 & Aleksandar Radujkovic 1 & Maria-Luisa Schubert 1 & Paul Schnitzler 2 & Tilman Schöning 3 & Carsten Müller-Tidow 1 & Ute Hegenbart 1 & Stefan O. Schönland 1 & Thomas Luft 1 & Peter Dreger 1 & Michael Schmitt 1 Received: 24 September 2020 / Accepted: 23 November 2020 # The Author(s) 2020
Abstract Morbidity and mortality after allogeneic hematopoietic cell transplantation (alloHCT) are still essentially affected by reactivation of cytomegalovirus (CMV). We evaluated 80 seropositive patients transplanted consecutively between March 2018 and March 2019 who received letermovir (LET) prophylaxis from engraftment until day +100 and retrospectively compared them with 80 patients without LET allografted between January 2017 and March 2018. The primary endpoint of this study was the cumulative incidence (CI) of clinically significant CMV infection (CS-CMVi) defined as CMV reactivation demanding preemptive treatment or CMV disease. With 14% CI of CS-CMVi at day +100 (11 events) was significantly lower in the LET cohort when compared to the control group (33 events, 41%; HR 0.29; p < 0.001). Whereas therapy with foscarnet could be completely avoided in the LET group, 7 out of 80 patients in the control cohort received foscarnet, resulting in 151 extra in-patient days for foscarnet administration (p = 0.002). One-year overall survival was 72% in the control arm vs 84% in the LET arm (HR 0.75 [95%CI 0.43–1.30]; p < 0.306). This study confirms efficacy and safety of LET for prophylaxis of CS-CMVi after alloHCT in a real-world setting, resulting in a significant patient benefit by reducing hospitalization needs and exposure to potentially toxic antiviral drugs for treatment of CMV reactivation. Keywords Letermovir . Cytomegalovirus . Real-world data . Hematopoietic-cell transplantation . Resource utilization
Introduction Cytomegalovirus (CMV) reactivation contributes significantly to morbidity and mortality after allogeneic hematopoietic cell transplantation (alloHCT) [1–4]. As per current guidelines, the standard approach for preventing CMV-related complications is based on continuous monitoring of CMV viremia, triggering initiation of preemptive therapy (PET) upon detection of CMV reactivation [5, 6]. PET comprises antiviral agents like ganciclovir, valganciclovir, and foscarnet. However, these agents are
* Patrick Derigs [email protected] 1
Department of Internal Medicine V (Hematology/Oncology/ Rheumatology), Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
2
Center for Infectious Diseases, Virology, Heidelberg University Hospital, Heidelberg, Germany
3
Department of Pharmacy, Heidelberg University Hospital, Heidelberg, Germany
associated with significant adverse effects such as myelo- or nephrotoxicity [7, 8], precluding their routine use for CMV prophylaxis. Accordingly
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