Letermovir for Cytomegalovirus prophylaxis in pediatric hematopoietic stem cell transplantation

Pediatr Blood Cancer. 2023 Nov;70(11):e30608. doi: 10.1002/pbc.30608. Epub 2023 Aug 7.

Abstract

Background: Letermovir (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.

Procedure: This 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).

Results: We 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.

Conclusions: In this retrospective study, the use of LTV prophylaxis in pediatric stem cell patients was associated with reduced clinically significant CMV DNAemia through D+180.

Keywords: Cytomegalovirus; letermovir; pediatric; prophylaxis.

MeSH terms

  • Adult
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use
  • Child
  • Cohort Studies
  • Cyclosporins* / pharmacology
  • Cyclosporins* / therapeutic use
  • Cytomegalovirus
  • Cytomegalovirus Infections* / drug therapy
  • Cytomegalovirus Infections* / etiology
  • Cytomegalovirus Infections* / prevention & control
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Retrospective Studies
  • Transplant Recipients
  • Voriconazole

Substances

  • letermovir
  • Voriconazole
  • Antiviral Agents
  • Cyclosporins