Single-center experience with use of letermovir for CMV prophylaxis or treatment in thoracic organ transplant recipients.
Acetates
/ administration & dosage
Adult
Aged
Antibiotic Prophylaxis
/ methods
Antiviral Agents
/ administration & dosage
Cytomegalovirus
/ drug effects
Cytomegalovirus Infections
/ blood
DNA, Viral
/ blood
Female
Graft Rejection
/ immunology
Heart Transplantation
/ adverse effects
Humans
Immunosuppressive Agents
/ adverse effects
Lung Transplantation
/ adverse effects
Male
Middle Aged
Quinazolines
/ administration & dosage
Secondary Prevention
/ methods
Transplant Recipients
/ statistics & numerical data
Treatment Outcome
cytomegalovirus
heart transplantation
letermovir
lung transplantation
Journal
Transplant infectious disease : an official journal of the Transplantation Society
ISSN: 1399-3062
Titre abrégé: Transpl Infect Dis
Pays: Denmark
ID NLM: 100883688
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
received:
15
02
2019
revised:
23
07
2019
accepted:
25
08
2019
pubmed:
6
9
2019
medline:
1
5
2020
entrez:
6
9
2019
Statut:
ppublish
Résumé
Cytomegalovirus (CMV) infection is common in thoracic organ transplant recipients. Valganciclovir and ganciclovir are used for both prophylaxis and treatment of this infection, but intolerance and treatment failure are common. Letermovir has been demonstrated to reduce the risk of CMV infection when used for prophylaxis in allogeneic hematopoietic cell transplantation. However, there are no data on its efficacy in thoracic organ transplantation. We examined the use of letermovir for either CMV prophylaxis (primary and secondary) or treatment in heart and lung transplant recipients at our institution from February 1, 2018, through December 31, 2018. Nine total patients received letermovir at our institution (8 lung transplant, 1 heart transplant) during the study period. Letermovir was prescribed for CMV prophylaxis in eight patients (primary prophylaxis in two patients and secondary prophylaxis in 6 patients), and for treatment of CMV DNAemia in two cases. One patient received letermovir for both secondary prophylaxis and treatment on separate occasions. Three out of 8 (37.5%) patients receiving letermovir for prophylaxis developed CMV DNAemia during prophylaxis. One patient treated for CMV disease had clinical failure with a sharp rise in serum CMV DNA PCR. The other patient treated for low-grade CMV DNAemia initially had a slight rise in CMV DNA PCR, but has since had a sustained response. No major side effects were experienced, and 2 patients reported minor side effects. Letermovir was well tolerated with only minor side effects reported; however, the rate of development of CMV DNAemia on prophylaxis was considerable. Further study of the dosing and efficacy of letermovir for CMV prophylaxis or treatment in thoracic organ transplant recipients is warranted.
Sections du résumé
BACKGROUND
BACKGROUND
Cytomegalovirus (CMV) infection is common in thoracic organ transplant recipients. Valganciclovir and ganciclovir are used for both prophylaxis and treatment of this infection, but intolerance and treatment failure are common. Letermovir has been demonstrated to reduce the risk of CMV infection when used for prophylaxis in allogeneic hematopoietic cell transplantation. However, there are no data on its efficacy in thoracic organ transplantation.
METHODS
METHODS
We examined the use of letermovir for either CMV prophylaxis (primary and secondary) or treatment in heart and lung transplant recipients at our institution from February 1, 2018, through December 31, 2018.
RESULTS
RESULTS
Nine total patients received letermovir at our institution (8 lung transplant, 1 heart transplant) during the study period. Letermovir was prescribed for CMV prophylaxis in eight patients (primary prophylaxis in two patients and secondary prophylaxis in 6 patients), and for treatment of CMV DNAemia in two cases. One patient received letermovir for both secondary prophylaxis and treatment on separate occasions. Three out of 8 (37.5%) patients receiving letermovir for prophylaxis developed CMV DNAemia during prophylaxis. One patient treated for CMV disease had clinical failure with a sharp rise in serum CMV DNA PCR. The other patient treated for low-grade CMV DNAemia initially had a slight rise in CMV DNA PCR, but has since had a sustained response. No major side effects were experienced, and 2 patients reported minor side effects.
CONCLUSION
CONCLUSIONS
Letermovir was well tolerated with only minor side effects reported; however, the rate of development of CMV DNAemia on prophylaxis was considerable. Further study of the dosing and efficacy of letermovir for CMV prophylaxis or treatment in thoracic organ transplant recipients is warranted.
Substances chimiques
Acetates
0
Antiviral Agents
0
DNA, Viral
0
Immunosuppressive Agents
0
Quinazolines
0
letermovir
1H09Y5WO1F
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13166Informations de copyright
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Razonable RR, Limaye RR. Cytomegalovirus infection after solid organ transplantation. In: Bowden RA, Ljungman P, Snydman DR, eds. Transplant Infections, 3rd edn. Philadelphia, PA: Lippincott Williams and Wilkins; 2010:328.
Bowman LJ, Melaragno JI, Brennan DC. Letermovir for the management of cytomegalovirus infection. Expert Opin Investig Drugs. 2017;26(2):235-241.
Stoelben S, Arns W, Renders L, et al. Preemptive treatment of Cytomegalovirus infection in kidney transplant recipients with letermovir: results of a phase 2a study. Transpl Int. 2014;27(1):77-86.
Avery RK, Arav-Boger R, Marr KA, et al. Outcomes in transplant recipients treated with foscarnet for ganciclovir-resistant or refractory cytomegalovirus infection. Transplantation. 2016;100(10):e74-e80.
Marty FM, Ljungman P, Chemaly RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med. 2017;377:2433-2444.
https://www.clinicaltrials.gov/ct2/show/NCT03443869?term=letermovir&rank=3. Accessed January 30, 2019.
Kaul DR, Stoelben S, Cober E, et al. First report of successful treatment of multidrug-resistant cytomegalovirus disease with the novel anti-CMV compound AIC246. Am J Transplant. 2011;11(5):1079-1084.
Cherrier L, Nasar A, Goodlet KJ, Nailor MD, Tokman S, Chou S. Emergence of letermovir resistance in a lung transplant recipient with ganciclovir-resistant cytomegalovirus infection. Am J Transpl. 2018;18:3060-3064.
Chong PP, Teiber D, Prokesch BC, et al. Letermovir successfully used for secondary prophylaxis in a heart transplant recipient with ganciclovir-resistant cytomegalovirus syndrome (UL97 mutation). Transpl Infect Dis. 2018;20:e12965.