Letermovir for Cytomegalovirus Prevention in Patients Undergoing Hematopoietic Cell Transplantation

Cytomegalovirus (CMV) is a double-stranded DNA virus that infects (seropositive on screening) more than half of adults by age 40. However, reactivation of detectable viral load (CMV reactivation) typically occurs only in immunocompromised patients. Notably, CMV reactivation after allogeneic hematopoietic cell transplant (HCT) can increase treatment-related mortality almost 2-fold compared to patients who do not have reactivation. Historically, prevention of CMV reactivation mainly included the preemptive strategy of serial monitoring of viral load and initiating an antiviral once the viral load became elevated in an effort to prevent end-organ disease. The major limitations of the antiviral agents utilized in preemptive therapy are myelosuppression and renal toxicity. In 2017, a first-in-class viral terminase complex subunit inhibitor, letermovir, became the only U.S. Food & Drug Administration-approved medication to prevent CMV reactivation after allogeneic HCT (e.g., as prophylaxis). In a phase III trial, patients who were randomized to letermovir prophylactically had decreased rates of CMV viremia leading to preemptive therapy. The purpose of this article is to describe the need for safe and effective medication to prevent CMV reactivation, the clinical efficacy of letermovir, and the impact oncology advanced practitioners can play in reducing CMV reactivation in patients undergoing allogeneic HCT.