Letermovir (LMV) is licensed for prophylaxis of CMV infection in allogeneic hematopoietic cell transplant adult CMV-seropositive patients. Due to its favorable safety profile, LMV brings potential for use in other clinical situations, outside the approved indication. The objective of the study was to analyze the efficacy and safety of the use of LMV in off-label indications in EBMT centers. A total of 49 patients were reported including 44 adults and 5 children. LMV was administered for: secondary prophylaxis (37 adults, 3 children), primary prophylaxis (2 children), pre-emptive treatment (5 adults), and therapy of CMV disease (2 adults; pneumonia, colitis). Cyclosporine was concomitantly used in 26 patients. Overall, LMV was used for a median 112 days (range: 10-473). Cumulative incidence of breakthrough infections during secondary prophylaxis was 10.1% (95% CI = 3.1-21.9). Prophylactic treatment with LMV resulted in 94.9% (95% CI = 81.0-98.7), and 81.9% (95% CI = 65.7-90.9) probability of, respectively, 60 and 120-day survival without CMV infection in patients receiving secondary prophylaxis. During therapy of CMV infection/disease, probability of 60 and 120-day overall survival was 100% and 71.4% (95% CI = 25.8-92.0), respectively. No breakthrough infection occurred in children on LMV prophylaxis. Adverse events were reported in 15/49 (30.4%) patients: the most common being nausea/vomiting (22.4%). In conclusion, the efficacy of the use of LMV as secondary prophylaxis was high, and the preliminary experience with the use of LMV for the treatment of patients with refractory CMV infection/disease was positive. Our data showed that higher dose or prolonged therapy did not result in increased rate of adverse events.

Attikon University General Hospital Athens Greece

Birmingham Heartlands Hospital Birmingham UK

Department for Cellular Therapy and Allogeneic Stem Cell Transplantation Karolinska University Hospital Huddinge Stockholm Sweden

Department of Hematology and Hematopoietic Cell Transplantation Medical University Poznan Poland

Department of Hematology and Oncology University Hospital Pilsen Pilsen Czech Republic

Department of Hematology Radboud University Center Nijmegen Nijmegen The Netherlands

Department of Histology and Embryology Faculty of Medicine Pilsen Czech Republic

Department of Pediatric Hematology and Oncology Collegium Medicum Nicolaus Copernicus University Torun Bydgoszcz Poland

Department of Pediatric Oncology Hematology Cell and Gene therapy IRCCS Bambino Gesu' Pediatric Hospital Rome Italy

Division of Hematology Department of Medicine Huddinge Karolinska Institutet Stockholm Sweden

Division of Infectious Diseases University of Genoa and IRCCS Ospedale Policlinico San Martino Genova Italy

Division of Pediatric Hematology Oncology and Stem Cell Transplantation Helsinki University Hospital Helsinki Finland

Division of Pediatric Hematology Oncology and Stem Cell Transplantation University of Padova Padova Italy

Divisions of Hematology and Internal Medicine Department of Medicine University Hospital Basel Basel Switzerland

EBMT Data Office Dept of Medical Statistics and Bioinformatics Leiden Netherlands

Hematology ICANS Strasbourg France

Hospital Clínico Universitario INCLIVA University of Valencia Valencia Spain

Hospital de la Princesa Madrid Spain

Hospital U Marqués de Valdecilla Santander Spain

Infectious Disease Research Program Center for Bone Marrow Transplantation and Department of Pediatric Hematology and Oncology University Children's Hospital Muenster Muenster Germany

Onco Ematologia Pediatrica Torino Italy

Pediatric Hematology Oncology Verona Italy

Service d'hématologie greffe Hôpital Saint Louis Université Paris Diderot 75010 Paris France

Universitaet Rostock Rostock Germany

University Regensburg Regensburg Germany

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