Improved Tolerability of De Novo Letermovir Over Valganciclovir for Cytomegalovirus Prophylaxis in Seropositive Liver Transplant Recipients

INTRODUCTION: Cytomegalovirus (CMV) can drive negative outcomes after liver transplant (LT). Though valganciclovir (VGC) remains the guideline-recommended standard-of-care, letermovir (LTV) may be beneficial in LT given reduced bone marrow suppression. METHODS: Adult patients receiving a LT with moderate-risk CMV serostatus (R+) 6/1/2021-9/30/2024 were evaluated. Patients were assigned to a cohort based on de novo antiviral prophylaxis regimen: VGC or LTV. The primary objective was tolerability and safety of LTV compared to VGC. RESULTS: Eighty-five patients met inclusion criteria: 60 in VGC and 25 in LTV cohorts. Significantly more patients in the LTV cohort completed antiviral prophylaxis (VGC 68.3% vs. LTV 92.0%, p = 0.02), with conversion to an alternative strategy occurring a median of 58 days post-LT in the VGC cohort. No patients terminated LTV due to intolerance or breakthrough. Patients in the VGC cohort were more likely to experience post-LT leukopenia (VGC 81.7% vs. LTV 52.0%, p = 0.005) and neutropenia (VGC 50.0% vs. LTV 24.0%, p = 0.03), as well as require GCSF support (VGC 25.0% vs. LTV 4.0%, p = 0.024). Patients in the LTV cohort tolerated significantly higher total daily doses (TDD) of mycophenolate at 3 (VGC 1750 mg vs. LTV 2000 mg, p = 0.005) and 6 (VGC 1000 mg vs. LTV 2000 mg, p = 0.04) months post-LT. Incidence of CMV viremia and acute rejection through 1-year post-LT was not significantly different between cohorts. CONCLUSION: De novo LTV for CMV prophylaxis in seropositive LT recipients appears to be safe and efficacious. LTV is more likely to be completed compared to VGC and is associated with less myelosuppressive toxicity, allowing for higher doses of mycophenolate. Future studies are needed to definitively evaluate the impact of LTV on rejection rates and transplant outcomes.