Immunovirology of cytomegalovirus infection in allogeneic stem cell transplant recipients undergoing prophylaxis with letermovir: A narrative review.
Carlos SolanoEstela GiménezEliseo AlbertJosé Luis PiñanaDavide NavarroPublished in: Journal of medical virology (2023)
On November 7, 2017, the US Food and Drug Administration approved the use of letermovir (LMV) for prophylaxis of cytomegalovirus (CMV) infection in adult CMV-seropositive allogeneic stem cell transplant recipients. After 6 years of use, a large body of real-world experience has been accumulated that validates the Phase III clinical trial results, in which LMV was shown to significantly reduce the risk of clinically significant CMV infection-defined as CMV end-organ disease or CMV DNAemia requiring pre-emptive antiviral therapy (PET)-and increase survival up to Week 24 after treatment inception. Notwithstanding, several issues still need to be settled, thus further investigation is required. First, since viral DNA may accumulate as a result of LMV-driven abortive CMV infection, what is the optimal viral load threshold in the blood that would prompt LMV prophylaxis interruption and PET inception? Should this be adapted to the patient's risk? Second, what is the impact of LMV prophylaxis on the reconstitution of functional CMV-specific T-cell responses? Would it be a wise approach to individually tailor the duration of LMV treatment according to the number of peripheral blood CMV-specific T cells at the end of regular prophylaxis? Third, how frequently do LMV-resistant strains arise while patients are on LMV prophylaxis and how could this be minimized? Here, we discuss the literature addressing these topics.
Keyphrases
- stem cells
- clinical trial
- phase iii
- peripheral blood
- stem cell transplantation
- drug administration
- computed tomography
- systematic review
- escherichia coli
- open label
- bone marrow
- end stage renal disease
- sars cov
- positron emission tomography
- ejection fraction
- peritoneal dialysis
- double blind
- study protocol
- low dose
- circulating tumor
- chronic kidney disease
- prognostic factors
- young adults
- high dose
- epstein barr virus
- combination therapy
- pet imaging
- cell therapy
- mesenchymal stem cells
- human health