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Letermovir
Letermovir is an antiviral medication approved for the prevention of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients of allogeneic hematopoietic stem cell transplants (HCT). It functions by inhibiting the CMV DNA terminase complex, a mechanism distinct from other antivirals like ganciclovir or valganciclovir.
Clinical Efficacy and Applications
In Hematopoietic Stem Cell Transplantation (HCT)
Recent studies have demonstrated that letermovir prophylaxis significantly reduces the incidence of clinically significant CMV infections (CS-CMVi) in CMV-seropositive HCT recipients. A retrospective cohort study indicated that letermovir not only decreased CMV-related complications but also improved overall survival rates in these patients. The protective effects were observed up to day 200 post-transplantation, although the impact on mortality beyond day 100 remains less clear
In Solid Organ Transplantation
In the context of kidney transplantation, letermovir has been found to be non-inferior to valganciclovir for CMV prophylaxis in adult CMV-seronegative recipients who received organs from CMV-seropositive donors. Notably, letermovir was associated with a lower incidence of leukopenia or neutropenia compared to valganciclovir, suggesting a more favorable hematologic safety profile
In Pediatric and Adolescent Populations
Emerging data support the use of letermovir in pediatric, adolescent, and young adult patients undergoing allogeneic HCT. A single-center, retrospective analysis demonstrated that letermovir prophylaxis effectively prevented CMV infections in this population, with a safety profile comparable to that observed in adults .
Safety Profile and Resistance Considerations
Letermovir is generally well-tolerated, with a lower risk of myelosuppression compared to traditional antivirals like ganciclovir. However, breakthrough CMV infections have been reported, particularly in patients receiving concurrent immunosuppressive therapies such as corticosteroids or calcineurin inhibitors. In some cases, resistance mutations in the CMV UL56 gene have been identified, underscoring the importance of vigilant monitoring for CMV DNA levels and potential resistance during prophylaxis .
Conclusion
Letermovir represents a significant advancement in CMV prophylaxis, offering effective prevention of CMV infections with a favorable safety profile, particularly in hematopoietic stem cell and solid organ transplant recipients. Ongoing research continues to refine its use across diverse patient populations, including pediatric and high-risk groups.
