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Simple Summary  Cytomegalovirus (CMV) infection and graft versus host disease (GVHD) both contribute to increased morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). Since the development of GVHD can increase a patient’s risk of developing CMV infection post-allo-HCT, the aim of our retrospective study was to assess the effectiveness of letermovir prophylaxis in preventing CMV infection in these patients at high risk for CMV reactivation. Letermovir is an antiviral approved for the prevention of CMV infection. This study demonstrated that patients with GVHD had significantly fewer CMV infections when they received letermovir prophylaxis compared to patients who did not receive letermovir.    Abstract  Cytomegalovirus (CMV) is the most clinically significant infection after allogeneic hematopoietic-cell transplantation (allo-HCT) and is associated with increased mortality. The risk for CMV reactivation increases with graft versus host disease (GVHD). GVHD contributes to significant morbidity and mortality and is treated with immunosuppressive therapies that can further increase CMV infection risk. Prophylaxis with letermovir, an oral antiviral approved to prevent CMV, has been shown to decrease the incidence of CMV infection post-allo-HCT in patients at high risk of CMV reactivation, but there is a lack of data confirming this benefit in patients with GVHD. In this single-center, retrospective study, we assessed the incidence of clinically significant CMV infection (CS-CMVi) in allo-HCT patients who received letermovir prophylaxis ( n  = 119) and who developed aGVHD compared to a control group ( n  = 143) who did not receive letermovir. Among aGVHD patients, letermovir prophylaxis decreased CS-CMVi in patients with aGVHD (HR 0.08 [95% CI 0.03–0.27],  p  < 0.001), reduced non-relapsed mortality ( p  = 0.04) and improved overall survival ( p  = 0.04). This data suggests that letermovir prophylaxis improves outcomes by preventing CS-CMVi in patients with aGVHD.

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Letermovir Prophylaxis and Cytomegalovirus Reactivation in Adult Hematopoietic Cell Transplant Recipients with and without Acute Graft Versus Host Disease