*Purpose: Letermovir is a new antiviral recently approved for cytomegalovirus (CMV) prophylaxis in CMV-seropositive hematopoietic-cell transplant recipients. Its off-label use in solid organ transplant (SOT) recipients has not been documented.

*Methods: We retrospectively identified all patients who had a SOT who received letermovir for CMV management in our center from December 2017 through November 2018. We collected clinical and virological data and assessed details of letermovir treatment.

*Results: Nine patients who underwent SOT and received letermovir were identified. All patients were CMV D+/R-. Their median age was 58 years, 5 were female. Four were kidney, 3 lung, and 2 heart transplantation recipients. Eight patients had experienced prior CMV viremia (2 were diagnosed with CMV disease); one patient received letermovir for primary prophylaxis. Letermovir was used for secondary prophylaxis due to severe leukopenia while on valganciclovir treatment in 8 (6 wild type CMV, 2 ganciclovir-resistant CMV due to UL97 mutations), and for CMV viremia treatment due to documented UL97 antiviral resistance in 1 patient. The median duration of letermovir administration was 88 days (range, 2-133), at a dose of 480 mg/day. Five patients started letermovir when CMV was detected below the limit of quantitation (<137 UI/mL). Seven of 8 patients who received letermovir secondary prophylaxis maintained CMV suppression for a median of 95 days (range, 2-133) while on letermovir. One patient developed quantifiable viremia within a week of starting letermovir and was switched to valganciclovir, and another patient died 2 days after starting letermovir due to other causes. In the one case of letermovir treatment of active CMV viremia, the infection became refractory to treatment and letermovir was discontinued after 85 days. In 8 out of 9 cases the patient’s absolute neutrophil count increased while on letermovir treatment. No patient experienced adverse events attributable to letermovir. Of 5 patients who successfully completed letermovir prophylaxis, one developed CMV retinitis 6 months after discontinuing letermovir while on high-dose valacyclovir prophylaxis.

*Conclusions: The data presented suggests that letermovir prophylaxis may have a role in secondary CMV prophylaxis in SOT recipients who experience adverse effects from other anti-CMV antivirals and require further treatment.

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