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

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:

• Letermovir
• CMV prophylaxis
• drug interaction
• CMV reactivation
• CMV terminase complex

Article highlights

• A phase 3 trial in recipients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) demonstrated that letermovir (LET) reduced clinically significant human cytomegalovirus (CMV) infection.

• LET targets the pUL56 subunit of the CMV terminase enzyme complex, which explains its minimal cross-resistance with conventional anti-CMV agents.

• When LET is administered in combination with the immunosuppressant drug cyclosporine, its daily dose is reduced from 480 mg to 240 mg due to drug interaction.

• The clinical benefit of prophylactic LET administration beyond post-transplant day 100, and that of treatment for asymptomatic CMV viremia and developed CMV disease, should be assessed in further investigations.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this paper has been a consultant for MSD for letermovir in allogeneic HCT and has participated in conferences or seminars related to the management of CMV in Allo-HCT patients with MSD support.

Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.