Real-world experience with letermovir for cytomegalovirus-prophylaxis after allogeneic hematopoietic cell transplantation: A multi-centre observational study.

Efficacy and safety of letermovir as prophylaxis for clinically significant cytomegalovirus infections (csCVMi) was evaluated in randomized controlled trials while most of the real-world studies are single-centre experiences. We performed a retrospective, multi-centre case-control study at six German university hospitals to evaluate clinical experiences in patients receiving CMV prophylaxis with letermovir (n = 200) compared to controls without CMV prophylaxis (n = 200) during a 48-week follow-up period after allogeneic hematopoietic cell transplantation (aHCT). The incidence of csCMVi after aHCT was significantly reduced in the letermovir (34%, n = 68) compared to the control group (56%, n = 112; p < 0.001). Letermovir as CMV prophylaxis (OR 0.362) was found to be the only independent variable associated with prevention of csCMVi. Patients receiving letermovir showed a significantly better survival compared to the control group (HR = 1.735, 95% CI: 1.111 - 2.712; p = 0.014). Of all csCMVi, 46% (n = 31) occurred after discontinuation of letermovir prophylaxis. Severe neutropenia (<500 neutrophils / µL) on the day of the stem cell infusion was the only independent variable for an increased risk of csCMVi after the end of letermovir prophylaxis. Our study highlights the preventive effects of letermovir on csCMVi after aHCT. A substantial proportion of patients developed a csCMVi after discontinuation of letermovir. In particular, patients with severe neutropenia require specific attention after drug discontinuation.

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Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SMH received travel grants from Tillotts. SMWH has received research and travel grants from Astellas, Merck, and Tillotts; research grants from Basilea, Gilead, and 3M; travel grants from Pfizer, and lecture honoraria from Astellas, Merck, and Tillotts. IWB participated on an advisory board on infection disease treatment in haematology patients by MSD. GB has received research grants from Novartis, honoraria from BMS, Gilead, Jazz, Novartis, Otsuka, and travel grants from Gilead and Jazz. SK has received speaker or consulting fees from BMS, Jazz Pharmaceuticals, Novartis Pharma GmbH, AstraZeneca, Janssen Pharmaceutica, GSK, Pentixapharm. OP has no conflicts of interest directly related to this work. OP has received honoraria or travel support from Gilead, Jazz, MSD, Neovii, Novartis, Pfizer and Therakos. He has received research support from Incyte and Priothera. He is member of advisory boards to Equillium Bio, Jazz, Gilead, Novartis, MSD, Omeros, Priothera, Sanofi, Shionogi and SOBI. OP acknowledges the support of José Carreras Leukämie-Stiftung (3R/2019, 23R/2021), Deutsche Krebshilfe (70113519), Deutsche Forschungsgemeinschaft (PE 1450/7-1, PE 1450/9-1, PE 1450/10-1) and Stiftung Charité BIH (BIH_PRO_549, Focus Group Vascular Biomedicine). ARR has received grants from DFG Walter Benjamin-Stipendium, unrelated to this work (no support for the present manuscript). DT has received research grants from Gilead Sciences, speaker or consulting fees from Abbvie, AstraZeneca, Gilead, Jazz, Merck/MSD, Noscendo, Novartis, Octapharma, Pfizer, Sanofi, Takeda, & Tillotts, and travel support from Abbvie, Gilead, Jazz, Medac, & Tillotts. MJGTV has received research grants from 3M, Astellas Pharma, Biontech, DaVolterra, Evonik, Gilead Sciences, Glycom, Immunic, MaaT Pharma, Merck/MSD, Organobalance, Seres Therapeutics, Takeda Pharmaceutical and speaker or consulting fees from Astellas Pharma, Basilea, Bio-Mérieux, DaVolterra, Farmak International Holding GmbH, Ferring, Gilead Sciences, Immunic AG, MaaT Pharma, Merck/MSD, Pfizer, Roche, Organobalance, SocraTec R&D GmbH. SK has received speaker or consulting fees from BMS, Jazz Pharmaceuticals, Novartis Pharma GmbH, AstraZeneca, Janssen Pharmaceutica, GSK, Pentixapharm. CW has received consulting fees or travel support from Takeda, mundipharma and Jazz Pharmaceuticals. JJV received research grants from Merck/MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), German Federal Ministry of Education and Research (BMBF), Deutsches Zentrum für Luft- und Raumfahrt (DLR), University of Bristol, Rigshospitalet Copenhagen, German Network University Medicine, German Cancer Consortium (DKTK), German Federal Ministry of Health (BMG), European Union, speaker fees from Merck / MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), University Hospital Freiburg/ Congress and Communication, Academy for Infectious Medicine, University Manchester, German Society for Infectious Diseases (DGI), Ärztekammer Nordrhein, Ärztekammer Hessen, University Hospital Aachen, Back Bay Strategies, German Society for Internal Medicine (DGIM), Shionogi, Molecular Health, Netzwerk Universitätsmedizin, Janssen, NordForsk, Biontech, APOGEPHA, German Cancer Consortium (DKTK), University Hospital Oldenburg, and meeting and travel support from German Centre for Infection Research (DZIF),University Manchester, German Society for Infectious Diseases (DGI), University Hospital Aachen, German Society for Internal Medicine (DGIM), Netzwerk Universitätsmedizin, German Cancer Consortium (DKTK). AYC, CH, TSc, and TSt have no conflicts of interest.