Letermovir for Primary Cytomegalovirus Prevention in Haploidentical Stem Cell Transplant Recipients

Abstract

<h3>Introduction</h3> Cytomegalovirus (CMV) continues to be a leading cause of morbidity and mortality among recipients of allogeneic hematopoietic stem cell transplant (HSCT). Marty et al. demonstrated the utility of letermovir for primary prophylaxis. However, a majority of the population in their study (69.4%) received a matched-unrelated or a matched-sibling donor transplant. Therefore, data is limited on optimal CMV prophylaxis among haploidentical recipients. <h3>Objectives</h3> The primary objective of this study was incidence of CMV reactivation prior to and beyond day 100 among haploidentical HSCT recipients who received primary letermovir prophylaxis. Secondary endpoints included median time to reactivation, median time to engraftment, and non-relapse mortality. <h3>Methods</h3> We conducted a single-center retrospective analysis to evaluate the efficacy of letermovir as primary prophylaxis among CMV seropositive haploidentical recipients between May 2018 to December 2019. Patients received letermovir prophylaxis from day 16 to 100. Exclusion criteria included subjects with history of CMV end-organ disease within 6 months of HSCT, history of CMV viremia at any time prior to transplant, received either ganciclovir, valganciclovir, foscarnet, or cidofovir within 7 days of transplant. <h3>Results</h3> We identified 20 haploidentical HSCT recipients, median age 52 years, the majority of which received reduced-intensity conditioning therapy with fludarabine, cyclophosphamide, and total-body irradiation. Graft-versus-host disease prophylaxis included tacrolimus, mycophenolate mofetil, and post-transplant cyclophosphamide. CMV reactivation occurred in 5 patients before day 100 (25%) range (day 20 to 45). Of the remaining 15 patients, an additional 4 (27%) had CMV reactivation after letermovir was discontinued at day 100, range (day 117 to 156). Overall survival at 1 year was 79.2% and non-relapse mortality at 1 year was 12.5%. <h3>Conclusion</h3> Our study demonstrated the efficacy of letermovir as primary prophylaxis among CMV seropositive haploidentical recipients. However, significant CMV reactivation was seen beyond day 100 and future studies need to be conducted on the ideal duration of prophylaxis in this high-risk population.