Efficacy and Safety of Letermovir for Cytomegalovirus Prophylaxis in Pediatric Hematopoietic Stem Cell Transplantation Recipients: A Systematic Review, Meta‐Analysis, and Meta‐Regression

ABSTRACT Objective Letermovir (LTV) is a novel antiviral agent approved by the FDA in 2017 for CMV prophylaxis in adult CMV‐seropositive allogeneic hematopoietic stem cell transplantation (allo‐HSCT) recipients and approved for pediatric use in 2024. This study systematically evaluates the efficacy and safety of LTV prophylaxis for CMV infection in pediatric allo‐HSCT recipients. Methods We systematically searched PubMed, Scopus, Web of Science, Embase, and Cochrane Library up to December 2024 for studies that evaluated the use of LTV prophylaxis in pediatric allo‐HSCT recipients. We conducted single‐arm meta‐analysis using Open Meta Analyst software and double‐arm meta‐analysis using R Studio. We pooled the dichotomous outcomes as event and total using the fixed‐effects model. Results Twelve articles were included in the analysis. The single‐arm meta‐analysis indicated that the prophylactic use of LTV against CMV among pediatrics was associated with a 10.9% (95% CI: 0.065, 0.153) infection rate without any disease occurrence. The percentage of patients who discontinued the drug due to adverse reactions was only 2.4% (95% CI: 0.003, 0.045), and all‐cause mortality was 7.9% (95% CI: 0.032, 0.126). The double‐arm meta‐analysis results indicated that the incidence of CMV infection was significantly lower in the LTV group in comparison to the control group (RR: 0.29; 95% CI: 0.16, 0.56; p < 0.001). Conclusion LTV has demonstrated safety and efficacy in preventing CMV infection and disease among high‐risk pediatric patients. Future large scale randomized trials are necessary to validate the findings.