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

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.