Letermovir for the prevention of cytomegalovirus infection in adult cytomegalovirus-seropositive hematopoietic stem cell transplant recipients

ABSTRACT

Introduction: Allogeneic hematopoietic cell transplants (allo-HCT) recipients are at the high-risk of reactivation of cytomegalovirus (CMV), and reactivation is associated with significant morbidity and mortality. Although available anti-CMV therapies may be effective for the prevention of CMV, they are plagued by unacceptable toxicities that prohibit their use in the post-transplant period. Recently studied CMV-active agents, such as maribavir and brincidofovir, failed to reduce the incidence of CMV infection in HCT recipients. Letermovir represents the first agent in the non-nucleoside 3,4 dihydro-quinazoline class of CMV viral terminase complex inhibitors, with activity solely against CMV. The positive results from the recently published Phase III study of letermovir for prevention of CMV infection in CMV-seropositive allo-HCT recipients led to its approval as a prophylactic agent for CMV in multiple countries.

Areas covered: In this review, we will evaluate this novel agent with a focus on letermovir mechanism of action, pharmacokinetics and metabolism, clinical efficacy, and safety and toxicities.

Expert commentary: With the introduction of letermovir, prevention of CMV infection in allo-HCT recipients may shift considerably, from a predominantly preemptive strategy to one that utilizes this novel therapy for prophylaxis.

KEYWORDS:

• CMV disease
• CMV infection
• cytomegalovirus
• hematopoietic stem cell transplant
• letermovir
• prophylaxis

Declaration of interest

R Chemaly received grants from Merck, Chimerix, AiCuris, Novartis, Shire, Oxford and received honoraria from Chimerix, Astellas, Oxford Immunotec, Merck, and MSD. R Chemaly was a principal investigator on the phase 2 and 3 trials for letermovir. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript discloses they are currently, and have been, a site PI for multiple clinical trials of investigational new anti–CMV drugs, including letermovir, maribavir, brincidofovir, and a CMV vaccine. They do not receive any personal remuneration from any pharmaceutical entity, and all funds for clinical trials are for study support only.

Additional information

Funding

This paper was not funded.