Letermovir as Cytomegalovirus Prophylaxis in a Pediatric Cohort: A Retrospective Analysis

Kuhn, Alexis; Puttkammer, Jenna; Madigan, Theresa; Dinnes, Laura; Khan, Shakila P.; Ferdjallah, Asmaa; Kohorst, Mira A.

doi:10.1016/j.jtct.2022.10.005

Cited by 22 publications

(20 citation statements)

References 22 publications

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“…There have been four retrospective studies evaluating LTV prophylaxis in pediatric HCT patients 6–9 . Recently, a single‐center study completed in Taiwan described four children (9.2–17.8 years old) who received LTV for CMV prophylaxis, and no breakthrough CMV reactivation occurred during the prophylactic period 6 .…”

Section: Discussionmentioning

confidence: 99%

“…There have been four retrospective studies evaluating LTV prophylaxis in pediatric HCT patients. [6][7][8][9] Recently, a single-center study completed in Taiwan described four children (9.2-17.8 years old) who received LTV for CMV prophylaxis, and no breakthrough CMV reactivation occurred during the prophylactic period. 6 This was supported by another single-center study that found no clinically significant CMV infection while on LTV primary prophylaxis in 10 pediatric patient occurrences (10-17.6 years old).…”

Section: Discussionmentioning

confidence: 99%

“…4,5 Currently, the use of LTV in the pediatric HCT population is off-label, and has not been well described in literature. [6][7][8][9][10][11][12][13][14][15] Additionally, LTV has the potential for clinically relevant drug interactions that, to our knowledge, have not been well described. LTV is a moderate CYP3A4 inhibitor that can increase the serum concentration of calcineurin inhibitors and is also thought to induce CYP2C19 and/or CYP2C9, which are the enzymes responsible for metabolism of various medications used in patients who have received an HCT, including voriconazole.…”

Section: Letermovir (Ltv) Is An Antiviral With Exclusive Activity Aga...mentioning

confidence: 99%

“…LTV gained FDA approval in 2017 for prophylaxis of CMV infection and disease in adult CMV‐seropositive recipients of an allogeneic HCT 4,5 . Currently, the use of LTV in the pediatric HCT population is off‐label, and has not been well described in literature 6–15 . Additionally, LTV has the potential for clinically relevant drug interactions that, to our knowledge, have not been well described.…”

Section: Introductionmentioning

confidence: 99%

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Letermovir for Cytomegalovirus prophylaxis in pediatric hematopoietic stem cell transplantation

Chen,

David,

Barthelmess

et al. 2023

Pediatric Blood & Cancer

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BackgroundLetermovir (LTV), an antiviral with exclusive activity against Cytomegalovirus (CMV), is approved for prophylaxis of CMV infection and disease in adult hematopoietic cell transplant (HCT) patients. The use of LTV in the pediatric HCT population is off‐label, and has limited literature to support its use.ProcedureThis was a single‐center, retrospective, matched (1:1 LTV:non‐LTV) cohort study of allogeneic HCT recipients transplanted at Children's Hospital Colorado from 2015 to 2022. The primary endpoint was clinically significant CMV DNAemia (defined as a CMV viral load >1000 copies/mL or any CMV DNAemia leading to preemptive treatment) through 6 months post transplant. Secondary outcomes included time to clinically significant CMV DNAemia, drug adverse effects, and dose adjustments of concomitant cyclosporine and voriconazole (known drug interactions).ResultsWe compared 41 patients who received LTV prophylaxis to 41 patients who received no CMV prophylaxis. There was less clinically significant CMV DNAemia through D+180 in the LTV group (9.8% vs. 17.0%, p = .33). Overall, LTV was well tolerated, and 87.8% of patients experienced no adverse effects related to the drug. There was no observed pattern in LTV effect on cyclosporine serum concentrations, but LTV was associated with decreased voriconazole trough levels.ConclusionsIn this retrospective study, the use of LTV prophylaxis in pediatric stem cell patients was associated with reduced clinically significant CMV DNAemia through D+180.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Letermovir (Ltv) Is An Antiviral With Exclusive Activity Aga...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Letermovir for Cytomegalovirus prophylaxis in pediatric hematopoietic stem cell transplantation

Chen,

David,

Barthelmess

et al. 2023

Pediatric Blood & Cancer

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“…There is solid evidence for the clinical efficacy of primary prophylaxis (also secondary) with LMV in preventing csCMV‐I and CMV end‐organ disease in adult CMV seropositive allo‐SCT patients and, to a much lesser extent, in pediatric patients, both in randomized trials and in a real‐life setting 13,48–81 . A comprehensive review and meta‐analysis on this subject was recently published 14 .…”

Section: Efficacy Of Lmv In Preventing Active CMV Infection and End‐o...mentioning

confidence: 99%

Immunovirology of cytomegalovirus infection in allogeneic stem cell transplant recipients undergoing prophylaxis with letermovir: A narrative review

Solano

Giménez

Albert

et al. 2023

Journal of Medical Virology

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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.

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Comment on: Letermovir for Cytomegalovirus prophylaxis in pediatric hematopoietic cell transplantation

Styczynski

2023

Pediatric Blood & Cancer

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Letermovir as Cytomegalovirus Prophylaxis in a Pediatric Cohort: A Retrospective Analysis

Cited by 22 publications

References 22 publications

Letermovir for Cytomegalovirus prophylaxis in pediatric hematopoietic stem cell transplantation

Letermovir for Cytomegalovirus prophylaxis in pediatric hematopoietic stem cell transplantation

Immunovirology of cytomegalovirus infection in allogeneic stem cell transplant recipients undergoing prophylaxis with letermovir: A narrative review

Comment on: Letermovir for Cytomegalovirus prophylaxis in pediatric hematopoietic cell transplantation

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