B362 - De Novo Letermovir for Cytomegalovirus Prophylaxis in Moderate-Risk Liver Transplant Recipients

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Author Block: H. Kleiboeker¹, J. Fose², C. Saddler³, D. Al-Adra³, J. Rice³, M. Jorgenson³, ¹Pharmacy, University of Wisconsin Health, Madison, WI, ²University of Wisconsin Hospital and Clinics, Madsison, WI, ³University of Wisconsin Hospital and Clinics, Madison, WI
*Purpose: Cytomegalovirus (CMV) drives negative outcomes after liver transplant (LT). Though valganciclovir (VGC) remains the guideline-recommended standard-of-care agent for CMV prophylaxis after LT, letermovir (LTV) has shown to be a favorable alternative given reduced bone marrow toxicity. The purpose of this study was to compare the use of LTV to standard-of-care VGC in CMV moderate risk liver transplant recipients.
*Methods: Adult patients receiving a CMV-seropositive LT between 6/1/2021 and 9/30/2024 were evaluated. Cohort (VGC or LTV) was assigned based on de novo antiviral prophylaxis regimen. The primary objective was safety and tolerability of VGC compared to LTV.
*Results: Eighty-five patients met inclusion criteria: 60 patients in VGC cohort and 25 patients in LTV cohort. Most patients underwent donation after brain death LT (VGC 91.7% vs. LTV 84.0%, p=0.68) with corticosteroid induction (91.7% vs. 92.0%, p=0.96) and D+/R+ serostatus (53.3% vs. 72.0%, p=0.11) [Table 1]. Significantly more patients in the LTV cohort completed antiviral prophylaxis (68.3% vs. 92.0%, p=0.02), with most patients in the VGC cohort converting to preemptive monitoring (84.2%). No patients terminated LTV due to intolerance or breakthrough viral replication. Patients in the VGC cohort were significantly more likely to experience post-LT leukopenia (81.7% vs. 52.0%, p=0.005) and neutropenia (50.0% vs 24.0%, p=0.03), as well as require GCSF during prophylaxis (25.0% vs 4.0%, p=0.024). Patients in the LTV cohort tolerated significantly higher total daily doses of mycophenolate at 3 (1750 vs 2000 mg, p=0.005) and 6 (1000 vs 2000 mg, p=0.04) months post-LT. No difference in graft function or rates of rejection were observed through 1-year post-LT.
*Conclusions: This study demonstrates that de novo LTV for CMV primary prophylaxis is safe and effective after moderate-risk LT. LTV prophylaxis is more likely to be completed than VGC and is associated with less myelosuppressive toxicity which allowed for higher doses of anti-metabolite immunosuppression and reduced healthcare resource utilization. Larger studies are needed to definitively evaluate the impact of LTV on rejection rates and transplant outcomes.