*Purpose: Letermovir (LMV) is approved for primary cytomegalovirus (CMV) prophylaxis in hematopoietic cell transplant recipients. Current FDA-approved antiviral options are limited to foscarnet and cidofovir for resistant CMV. Both are nephrotoxic and poorly tolerated. Limited data exist for LMV prophylaxis or treatment in solid-organ transplant (SOT) recipients.

*Methods: A retrospective analysis of SOT recipients receiving LMV for primary prophylaxis, maintenance and/or treatment of resistant/refractory CMV disease from 1/2018- 3/2019 was conducted. Patient characteristics, transplant variables, extent of CMV disease, prior antiviral use, and clinical outcomes are described.

*Results: 6 patients received LMV: 1 primary prophylaxis, 3 secondary prophylaxis, and 2 treatment. LMV was used for extended primary prophylaxis following 6 months of valganciclovir prophylaxis due to underlying telomere disease and associated risk for leukopenia as well as significant risk for CMV disease. Secondary prophylaxis with LMV was started following induction with foscarnet in Patient B. Rebound viremia developed 48 days after stopping LMV. Following re-induction with foscarnet, secondary prophylaxis with LMV resumed and CMV viral load remains undetectable. Patient C was switched from valganciclovir for severe leukopenia. Patient D was maintained on LMV secondary prophylaxis following initial treatment with ganciclovir. Breakthrough viremia occurred on Day 60 of LMV, with emergence of UL56 mutation conferring LMV resistance. He was treated with foscarnet, and achieved virologic suppression. CMV specific cell mediated immune assays (CMV lymphocyte proliferation assay and CMV Elispot) were conducted and resulted positive indicating immune reconstitution of CMV specific T cells. LMV was used for treatment of active CMV disease in 2 cases of bilateral lung transplantation: one due to leukopenia on valganciclovir and the other due presence of UL 97 and UL54 mutations. In both cases CMV subsequently developed UL56 mutations conferring LMV resistance, and LMV was discontinued. One patient maintained virologic suppression despite LMV resistance, and the other developed rebound viremia requiring foscarnet. All dosing was 480mg, and no adverse events were ascribed to LMV.

*Conclusions: LMV appears safe and effective for prophylaxis, including ganciclovir-resistant CMV. Rebound viremia occurred in treatment cases with subsequent UL56 resistance detection, thus LMV use for treatment should be used cautiously with close monitoring for breakthrough.

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