Letermovir for cytomegalovirus infection in allogeneic hematopoietic stem-cell transplantation: tips and notes for effective use in clinical practice

Expert Rev Anti Infect Ther. 2024 Apr;22(4):169-178. doi: 10.1080/14787210.2024.2322439. Epub 2024 Mar 1.

Abstract

Introduction: Cytomegalovirus (CMV) infection remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). While conventional antiviral agents such as ganciclovir can be used for CMV prophylaxis, toxicities such as myelosuppression are a major concern.

Area covered: This work aimed to summarize the latest information and practical issues regarding a new anti-CMV agent, letermovir (LET).

Expert opinion: LET inhibits CMV replication by binding to components of the DNA terminase complex. A phase 3 trial in allo-HSCT recipients showed a reduced incidence of clinically significant CMV infection in the LET group. In 2017, this agent was first approved for CMV prophylaxis in adult CMV-seropositive allo-HSCT recipients in the United States, and is now used worldwide. While LET has an excellent toxicity profile, there are issues to be aware of, such as interactions with other drug classes (e.g. immunosuppressants and antifungals) and reactivation of CMV infection following LET cessation. While LET is the current standard of care for CMV prophylaxis, there are no established protocols for preemptive treatment of asymptomatic CMV viremia or for treatment of developed CMV disease. Further research is needed to maximize the benefits of LET, including the discovery of biomarkers.

Keywords: CMV prophylaxis; CMV reactivation; CMV terminase complex; Letermovir; drug interaction.

Publication types

  • Review

MeSH terms

  • Acetates / therapeutic use
  • Adult
  • Antiviral Agents / therapeutic use
  • Clinical Trials, Phase III as Topic
  • Cytomegalovirus
  • Cytomegalovirus Infections* / drug therapy
  • Cytomegalovirus Infections* / etiology
  • Cytomegalovirus Infections* / prevention & control
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Quinazolines*

Substances

  • Acetates
  • Antiviral Agents
  • letermovir
  • Quinazolines