Letermovir for Prevention of Recurrent Cytomegalovirus in High-Risk Allogeneic Hematopoietic Cell Transplantation Recipients

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. (c) 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.