Extended letermovir administration, beyond day 100, is effective for CMV prophylaxis in patients with graft versus host disease

BACKGROUND: Cytomegalovirus (CMV) reactivation is associated with significant morbidity and mortality after an allogeneic hematopoietic cell transplant (AHCT), and graft versus host disease (GVHD) increases the risk of CMV reactivation. Letermovir is approved for CMV prophylaxis in CMV-seropositive patients, but has only been studied through day 100 post-transplantation in the registration trial. Its efficacy in preventing CMV in patients with GVHD requiring treatment beyond the day 100 milestone has not been studied. METHODS: We retrospectively analyzed all patients who underwent an AHCT at a single center over a period of 24 months, and identified a cohort of 20 patients who received extended duration of letermovir (beyond 100 days) after the diagnosis of GVHD. The primary end point was the incidence of clinically significant CMV infection, defined as onset of CMV disease or initiation of preemptive therapy with alternative antiviral agents. RESULTS: In this high-risk cohort, only one patient (5%) developed a clinically significant CMV infection, requiring preemptive therapy. No patients developed CMV organ disease. Three additional patients developed CMV viremia of ≥150 IU/mL while on letermovir and after the onset of GVHD, and none required additional treatment. Receipt of post-transplant cyclophosphamide (PTCy) and low CD4 count after the development of GVHD were associated with breakthrough CMV viremia while on extended duration letermovir. CONCLUSIONS: Extended duration letermovir was efficacious in preventing clinically significant CMV infections in patients with GVHD.