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

Cytomegalovirus (CMV) drives negative outcomes after liver transplant (LT), with patients having high-risk serostatuses (D+/R-) being especially vulnerable. While valganciclovir (VGC) remains the standard-of-care, letermovir (LTV) represents a promising potential in LT, given the reduced myelosuppression.

Adult patients receiving an LT with high-risk CMV serostatus (D+/R-) June 1, 2021-June 6, 2024 were evaluated. Patients were included in the standard-of-care (SOC) or LTV cohort based on de novo antiviral prophylaxis regimen. The primary objective was the safety and tolerability of VGC compared to LTV.

Sixty-one patients met inclusion criteria: 35 in SOC and 26 in LTV cohorts. A significantly higher proportion of patients in the LTV cohort completed antiviral prophylaxis (28.6% vs. 80.8%, p < 0.001), with most patients in the SOC cohort experiencing VGC intolerance (71.4%). No patients terminated LTV due to intolerance or breakthrough. Patients in the SOC cohort had lower white blood cell (1.6 vs. 2.75 × 10³ cells/mm3; p < 0.001) and absolute neutrophil (850 vs. 2260 cells/µL p = 0.003) nadir at 6 months. Significantly more patients in the SOC cohort required granulocyte-colony stimulating factor (57.1% vs. 15.4%, p < 0.001). Patients in the LTV cohort tolerated significantly higher doses of mycophenolate through 12 months post-transplant.

De novo LTV for primary prophylaxis after LT appears to be safe and effective. LTV is more likely to be successfully completed than the current SOC and is associated with less myelosuppressive toxicity, which allows maintenance of higher mycophenolate doses. Future studies are needed to evaluate the impact of LTV on rejection rates and transplant outcomes.