Clinically significant cytomegalovirus infection (CSI-CMV) is an important factor associated with mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). It is estimated that the incidence of CSI-CMV in the post-HSCT period is 30 percent to 70 percent in transplanted individuals. Therefore, CSI-CMV is considered a complication in allogeneic HSCT, which can trigger Cytomegalovirus disease (CMVD). Letermovir is an antiviral agent indicated especially for the prophylaxis of CMVD post-HSCT. The objective of this work was to evaluate the efficacy, effectiveness and safety of letermovir, comparing it with placebo or other existing prophylactic treatments.

A systematic review was carried out according to PRISMA 2020. A strategy was developed for searching electronic bibliographic databases. Retrieved publications were selected by a pair of reviewers. The same pair performed the data extraction. A qualitative assessment of the efficacy, effectiveness and safety of letermovir was performed.

Eighteen studies were included, being experimental and observational. Overall, the pivotal RCT demonstrates the efficacy of letermovir in reducing the incidence of CSI-CMV. However, there was no statistically significant difference in all-cause mortality and letermovir-related overall survival, events of graft versus host disease, neutropenia, acute kidney disease and 48-week mortality. Observational studies, in general, present results similar to those found in the pivotal RCT. The main adverse events associated with letermovir were peripheral edema (14.5%), vomiting (18.5%), headache (13.9%), cough (14.2%), abdominal pain (11.8%) and fatigue (13.4%).

The prophylactic use of letermovir in CMV-R+ patients after allogeneic HSCT demonstrates beneficial results in the prevention of CSI-CMV. However, there were no identified improvements for other outcomes. As for safety, it was observed that there is still little information about adverse events related to the drug, and studies assessing this aspect are needed for better comprehension.