Abstract
We evaluated letermovir (LTV) for secondary prophylaxis for cytomegalovirus (CMV) in allogeneic hematopoietic cell transplant recipients (HCT) at high-risk for CMV recurrence. This open-label study was conducted at Memorial Sloan Kettering Cancer Center and the University of Minnesota. Patients with clinically significant CMV infection (cs-CMVi) and ≥1 high-risk criteria for CMV who achieved viral suppression with standard CMV antivirals received LTV secondary prophylaxis for up to 14 weeks. The primary endpoint was cs-CMVi at week 14; secondary endpoints included LTV resistance, CMV end-organ disease (EOD), CMV-related death, and LTV-related adverse events at week 14. Thirty-six patients were analyzed (CMV seropositive, n = 33; T cell-depleted HCT, n = 25; cord blood allograft, n = 5). By week 14 post-transplantation, 5 patients met the primary endpoint of cs-CMVi, for a cumulative incidence of 14.9% (95% confidence interval, 2.6% to 27.1%). Four patients developed LTV breakthrough cs-CMVi (including 2 patients with confirmed LTV resistance). The remaining patient developed rebound cs-CMVi after premature discontinuation of LTV due to enrollment in a clinical trial. There were no cases of CMV EOD, CMV-related death, or LTV-related adverse events by week 14 or by week 24. Our data support that LTV secondary prophylaxis is safe and effective in high-risk HCT recipients.