Letermovir in Allogeneic Hematopoietic Cell Transplantation: Beyond the Label

Abstract

Background Cytomegalovirus (CMV) is associated with significant morbidity and mortality in allogeneic hematopoietic cell transplantation (allo-HCT) patients (pts). Cumulative incidence of CMV infection in high-risk patients such as CD34-selected or haploidentical HCT have been reported as high as 61.8-84.5% and 53-81%, respectively. Letermovir (LTV) was approved in 11/2017 for prophylaxis (ppx) in CMV-seropositive recipients (R+) of allo-HCT. Since 12/2017, LTV ppx was implemented at our center for both primary and secondary ppx. We report our real-world experience. Methods Adult CMV R+ allo-HCT pts who initiated LTV as primary or secondary prophylaxis were identified between 1/1/2018 and 6/30/18. Cord blood transplants were excluded. The primary outcome was the incidence of clinically significant CMV infection (CMV viremia requiring preemptive treatment or CMV disease). Pts were followed through 9/2018. Results 53 pts initiated LTV. 69.8% pts were at high risk for CMV reactivation and disease (primarily ex vivo T-cell depleted HCT [n = 18; 34%] or haploidentical T-replete HCT [n = 12; 22.6%]). Baseline characteristics are summarized in Table 1. 39 pts (73.5%) received LTV as primary ppx after HCT, with a median day of LTV initiation of D+7 (range D+7D+40). At LTV initiation, 34 pts had an undetectable CMV DNA, and 4 had CMV Conclusion Primary LTV ppx significantly reduced CMV reactivation, and high-risk patients may benefit from extended prophylaxis. In patients who received preemptive therapy for CMV, use of secondary ppx showed no recurrent CMV reactivation. LTV is well tolerated. Additional studies are needed to determine optimal ppx duration and to clarify role of secondary CMV ppx in high-risk allo-HCT. The future standard of care will likely include extended primary ppx and secondary ppx and result in decreased morbidity and mortality associated with CMV.