Efficacy and safety of letermovir for cytomegalovirus prophylaxis in thoracic organ transplantation: a systematic review and meta-analysis

OBJECTIVE: Letermovir (LTV) is a novel antiviral agent approved for cytomegalovirus (CMV) prophylaxis in high risk allogeneic hematopoietic stem cell transplantation. However, its efficacy and safety in thoracic organ transplant (TOT) recipients remain underexplored. This study systematically evaluates the efficacy and safety of LTV prophylaxis for CMV infection in TOT recipients. METHODS: A systematic search of PubMed, Scopus, Web of Science, Embase, and Cochrane Library was conducted up to February 2025. Studies assessing LTV prophylaxis in adult TOT were included. We performed a single-arm meta-analysis using Open Meta Analyst software and a double-arm meta-analysis with Review Manager. Dichotomous outcomes were pooled as event rates using the fixed-effects model. RESULTS: Eleven studies with 380 patients were included. The single-arm meta-analysis showed that LTV prophylaxis was associated with a 3.7% (95% CI: 0.006, 0.069) breakthrough CMV infection rate. The incidence of low-level CMV viremia was 15.8% (95% CI: 0.070, 0.245). The percentage of patients who discontinued LTV due to adverse effects was only 1.7% (95% CI: -0.002, 0.035), while 79.9% (95% CI: 0.610, 0.988) experienced improvement in leukopenia. The double-arm meta-analysis showed no statistically significant difference in breakthrough CMV infection rates between LTV and valganciclovir (VGC) (RR: 0.40; 95% CI: 0.09, 1.68; P = 0.21). CONCLUSION: LTV prophylaxis demonstrates promising efficacy and safety in reducing breakthrough CMV infection, low-level viremia, and adverse events in TOT recipients. Its favorable safety profile, particularly in mitigating leukopenia, highlights its potential as an effective alternative to VGC.