Letermovir Prophylaxis Versus Pre-Emptive Therapy for Cytomegalovirus after Hematopoietic Stem-Cell Transplantation

Introduction Cytomegalovirus (CMV) infection is one of the most common complication after allogeneic hematopoietic stem-cell transplantation (HSCT) still associated with significant morbidity and mortality. Although pre-emptive therapy (PET) are routinely used in treatment of CMV after SCT, their prophylactic use is limited by clinically unacceptable myelosuppression and nephrotoxicity. Letermovir, available since 2019 in Italy, is the first antiviral agent approved by FDA and EMA which is indicated for the prophylaxis of CMV infection in CMV seropositive (R+) patients undergoing SCT. Presently, cost and drug interactions are the main disadvantages of Letermovir use. We performed a single-center observational retrospective study to evaluate the efficacy of primary Letermovir prophylaxis for CMV infection among high-risk patients (R+) receiving HSCT from serological negative donor (D-). Methods We evaluated a cohort of R+/D- patients transplanted from January 2017 to December 2020 (86/235 transplanted patients): among those eligible for Letermovir prophylaxis (N=70), 29 patients (transplanted after 2019) received Letermovir until day +100, whereas 41 patients (the historical control group transplanted before 2019) received CMV PET only in case of increased viral load (CMV reactivation). Patients unable to take oral therapy at day +7 from HSCT or assuming drugs for concomitant clinical conditions bringing about major pharmacokinetic interaction were excluded (N=16). We compared day +100 and day +200 cumulative incidence of clinically significant CMV infection (CS-CMVi), defined according to drug registration trial: Letermovir discontinuation before day +100, CMV reactivation (CMV-DNAemia leading to PET), CMV tissue invasive disease, disease relapse and death from any causes. Survival functions between groups were estimated by the Kaplan-Meier method and compared using log-rank test. Moreover, the overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM) and cumulative incidence of II-IV grade acute graft-versus-host disease (aGVHD) was compared in the two cohorts. Finally, we analyzed the number of accesses in day hospital from initial discharge to day +180, as an indirect cost-effectiveness evaluation of letermovir prophylaxis. Results No severe adverse events related to the therapy were observed in the letermovir group. Letermovir prophylaxis started at a median of 11 days (range, 5-27) after HSCT. The median duration of Letermovir ad