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Letermovir for Prophylaxis and Pre-emptive Therapy of Cytomegalovirus Infection in Paediatric Allogeneic Haematopoietic Cell Transplant Patients

BACKGROUND: Cytomegalovirus (CMV) infection is a frequent event in patients undergoing allogeneic haematopoietic cell transplantation (HCT) and is associated with increased morbidity and mortality due to eventual progress to end-organ disease. Letermovir prophylaxis for CMV infections has become a s...

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Autores principales: Körholz, Katharina F., Füller, Miriam A., Hennies, Marc, Holterhus, Malcolm, Hagedorn, Susanne, Ahlmann, Martina, Thorer, Heike, Burkhardt, Birgit, Groll, Andreas H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931806/
https://www.ncbi.nlm.nih.gov/pubmed/36572834
http://dx.doi.org/10.1007/s40272-022-00547-6
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author Körholz, Katharina F.
Füller, Miriam A.
Hennies, Marc
Holterhus, Malcolm
Hagedorn, Susanne
Ahlmann, Martina
Thorer, Heike
Burkhardt, Birgit
Groll, Andreas H.
author_facet Körholz, Katharina F.
Füller, Miriam A.
Hennies, Marc
Holterhus, Malcolm
Hagedorn, Susanne
Ahlmann, Martina
Thorer, Heike
Burkhardt, Birgit
Groll, Andreas H.
author_sort Körholz, Katharina F.
collection PubMed
description BACKGROUND: Cytomegalovirus (CMV) infection is a frequent event in patients undergoing allogeneic haematopoietic cell transplantation (HCT) and is associated with increased morbidity and mortality due to eventual progress to end-organ disease. Letermovir prophylaxis for CMV infections has become a standard of care in adult HCT recipients due to its efficacy and high tolerability. However, it is not yet approved for paediatric patients. OBJECTIVE: In a retrospective single-centre observational study we evaluated the use of letermovir for prophylaxis or pre-emptive treatment of cytomegalovirus (CMV) infection in seropositive paediatric HCT recipients receiving the compound outside of clinical trials. The primary endpoint was CMV reactivation requiring a change of medication. METHODS: A total of 17 patients (seven female/ten male; median age 12.2 [range 3.5–19] years, median body weight 39.5 [range 15–63] kg; median follow-up time 463.7 [range 41–1022] days) were identified who were started on oral (14) or intravenous (3) followed by oral (2) letermovir shortly after neutrophil engraftment at doses determined on the basis of age, weight, and concomitant cyclosporine use. RESULTS: Five patients had no evidence of viral replication (prophylactic use), while 12 patients had varying extents of viral replication (pre-emptive therapy). A change of therapy was required in one patient due to a sustained increase in CMV viral load, and in two patients, letermovir was stopped without later reactivation after initiation of palliative care for recurrent leukaemia. Of the 14 patients who completed treatment, 3 had evidence of transient viral replication after end of treatment that required no further antiviral treatment. No patients (of 17) discontinued letermovir due to an adverse event. CONCLUSION: Letermovir was effective in controlling CMV infection in seropositive paediatric allogeneic HCT recipients and was overall well tolerated. Pending completion of the still ongoing paediatric investigation plans, letermovir will be an important adjunct to our options for control of infectious complications in this special population.
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spelling pubmed-99318062023-02-17 Letermovir for Prophylaxis and Pre-emptive Therapy of Cytomegalovirus Infection in Paediatric Allogeneic Haematopoietic Cell Transplant Patients Körholz, Katharina F. Füller, Miriam A. Hennies, Marc Holterhus, Malcolm Hagedorn, Susanne Ahlmann, Martina Thorer, Heike Burkhardt, Birgit Groll, Andreas H. Paediatr Drugs Original Research Article BACKGROUND: Cytomegalovirus (CMV) infection is a frequent event in patients undergoing allogeneic haematopoietic cell transplantation (HCT) and is associated with increased morbidity and mortality due to eventual progress to end-organ disease. Letermovir prophylaxis for CMV infections has become a standard of care in adult HCT recipients due to its efficacy and high tolerability. However, it is not yet approved for paediatric patients. OBJECTIVE: In a retrospective single-centre observational study we evaluated the use of letermovir for prophylaxis or pre-emptive treatment of cytomegalovirus (CMV) infection in seropositive paediatric HCT recipients receiving the compound outside of clinical trials. The primary endpoint was CMV reactivation requiring a change of medication. METHODS: A total of 17 patients (seven female/ten male; median age 12.2 [range 3.5–19] years, median body weight 39.5 [range 15–63] kg; median follow-up time 463.7 [range 41–1022] days) were identified who were started on oral (14) or intravenous (3) followed by oral (2) letermovir shortly after neutrophil engraftment at doses determined on the basis of age, weight, and concomitant cyclosporine use. RESULTS: Five patients had no evidence of viral replication (prophylactic use), while 12 patients had varying extents of viral replication (pre-emptive therapy). A change of therapy was required in one patient due to a sustained increase in CMV viral load, and in two patients, letermovir was stopped without later reactivation after initiation of palliative care for recurrent leukaemia. Of the 14 patients who completed treatment, 3 had evidence of transient viral replication after end of treatment that required no further antiviral treatment. No patients (of 17) discontinued letermovir due to an adverse event. CONCLUSION: Letermovir was effective in controlling CMV infection in seropositive paediatric allogeneic HCT recipients and was overall well tolerated. Pending completion of the still ongoing paediatric investigation plans, letermovir will be an important adjunct to our options for control of infectious complications in this special population. Springer International Publishing 2022-12-27 2023 /pmc/articles/PMC9931806/ /pubmed/36572834 http://dx.doi.org/10.1007/s40272-022-00547-6 Text en © The Author(s) 2022, corrected publication 2023 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Original Research Article
Körholz, Katharina F.
Füller, Miriam A.
Hennies, Marc
Holterhus, Malcolm
Hagedorn, Susanne
Ahlmann, Martina
Thorer, Heike
Burkhardt, Birgit
Groll, Andreas H.
Letermovir for Prophylaxis and Pre-emptive Therapy of Cytomegalovirus Infection in Paediatric Allogeneic Haematopoietic Cell Transplant Patients
title Letermovir for Prophylaxis and Pre-emptive Therapy of Cytomegalovirus Infection in Paediatric Allogeneic Haematopoietic Cell Transplant Patients
title_full Letermovir for Prophylaxis and Pre-emptive Therapy of Cytomegalovirus Infection in Paediatric Allogeneic Haematopoietic Cell Transplant Patients
title_fullStr Letermovir for Prophylaxis and Pre-emptive Therapy of Cytomegalovirus Infection in Paediatric Allogeneic Haematopoietic Cell Transplant Patients
title_full_unstemmed Letermovir for Prophylaxis and Pre-emptive Therapy of Cytomegalovirus Infection in Paediatric Allogeneic Haematopoietic Cell Transplant Patients
title_short Letermovir for Prophylaxis and Pre-emptive Therapy of Cytomegalovirus Infection in Paediatric Allogeneic Haematopoietic Cell Transplant Patients
title_sort letermovir for prophylaxis and pre-emptive therapy of cytomegalovirus infection in paediatric allogeneic haematopoietic cell transplant patients
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931806/
https://www.ncbi.nlm.nih.gov/pubmed/36572834
http://dx.doi.org/10.1007/s40272-022-00547-6
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