Letermovir for prevention of recurrent CMV in high-risk allogeneic hematopoietic cell transplant (HCT) recipients.

Background: We evaluated letermovir (LTV) for secondary prophylaxis for cytomegalovirus (CMV) in allogeneic hematopoietic cell transplant recipients (HCT) at high-risk for CMV recurrence.

Methods: Open-label study 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 letermovir (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 (AE) at week 14.

Results: Thirty-six patients were analyzed (CMV seropositive 33, T-cell depleted HCT 25, cord blood allograft 5) were analyzed. By week 14, 5 patients met the primary endpoint of cs-CMVi, for a cumulative incidence of 14.9% (95% confidence interval 2.6 - 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 or CMV-related deaths or LTV related AE by week 14 or by week 24.

Conclusions: Our data supports that LTV secondary prophylaxis is safe and effective in high-risk HCT recipients.