A076 - Letermovir vs Valganciclovir in CMV High Risk Liver Transplant Recipients

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Author Block: J. Dann, J. Geyston, T. Parpia, B. Wentworth, University of Virginia Health, Charlottesville, VA
*Purpose: Guidelines recommend valganciclovir (VGC) 900 mg daily for 3-6 months in high-risk patients (D+/R-). However, its use may cause significant leukopenia and there is growing interest in alternative prophylactic agents. Data supporting use of letermovir (LTV) is limited in liver transplant. Here we compare efficacy and tolerability of the standard of care, VGC, versus LTV in CMV D+/R- liver transplant recipients (LTR).
*Methods: Retrospective single-center study of adult high-risk CMV LTR transplanted between 11/2014-5/2025 receiving either VGC 900 mg daily vs LTV 480 mg daily for 3 months and who had 6 months of follow-up. The primary outcomes were quantifiable CMV DNAemia during prophylaxis and 6-months post-transplant. Secondary outcomes were leukopenia, neutropenia, leukopenia-related medication changes, and antiviral resistance. Statistical analysis included independent sample t-tests, χ2 , and Kaplan-Meier survival analysis with log rank test.
*Results: Fifty-six LTR were included (VGC: 47 / LTV: 9). The LTV group was younger and had higher MELD at transplant; induction immunosuppression regimens varied between groups as did time to initiation of prophylaxis. Rates of CMV DNAemia were similar during prophylaxis but there was more CMV DNAemia within 6 months of transplant in the LTV group (p=0.017). CMV resistance was rare overall; there was one case in the LTV group (a UL97 mutation). Patients receiving LTV experienced fewer episodes of leukopenia or neutropenia and required less granulocyte colony stimulating factor during the prophylaxis period.
*Conclusions: In an early single center experience, LTV was associated with significantly less cytopenias requiring medication adjustment. While there was a higher rate of CMV DNAemia at 6 months with LTV compared to VGC prophylaxis, these cases were uncomplicated. Longer-term study with a larger, more homogenous population is needed to assess if LTV is non-inferior to VGC in safety and efficacy. Nonetheless, our findings suggest LTV has good tolerability and may be a viable alternative in patients with increased risk for post-transplant leukopenia.