Real-Life Data on Efficacy and Safety of Letermovir for Primary Prophylaxis of Cytomegalovirus in Allogeneic Hematopoietic Stem Cell Recipients: Single-Center Analysis.

BACKGROUND: Cytomegalovirus (CMV) reactivation is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Introduction of letermovir (LMV) seems to improve post-transplant outcome, however delayed-onset CMV reactivations still remains a challenge.

PATIENTS AND METHODS: We retrospectively analyzed data of 93 adult CMV-seropositive recipients receiving LMV as CMV prophylaxis after HSCT for hematological malignancies between 2019 and 2023. Starting LMV dose was 480 mg daily, reduced to 240 mg daily in those with ciclosporin A (CsA) co-administration. CMV DNA in blood was measured using real time polymerase chain reaction (RT-PCR) weekly for the first 2 months after transplantation, then bi-weekly till the end of immunosuppressive treatment. LMV was continued to day +100 or to CMV reactivation.

RESULTS: Median recipient age at transplant was 51 years (range 20-71). All patients received grafts from peripheral blood, mostly for myeloid acute leukemias (60%). Median time from transplantation to LMV initiation was 3 days (range 0-24). 55% of patients were transplanted from matched related donors, 32% from unrelated donors whereas 13% underwent haploidentical HSCT. Four patients (4%) had CMV "blips" while on LMV, yet drug was continued and repeated assays were negative. Only 2 patients (2%) reactivated CMV while on LMV: on days 48 and 34 after HSCT, respectively. Seven patients (7%) developed late-onset CMV reactivation after median of 124 days after HSCT (range 118-152) and were successfully treated with ganciclovir (GCV). CMV disease was not observed. Grade III-IV acute graft-versus-host disease (aGVHD) occurred in 6 patients (6%) during LMV. LMV treatment was free of side effects.

CONCLUSIONS: LMV prophylaxis was effective in preventing CMV reactivation with favorable safety profile. CMV reactivation occurred mostly after LMV discontinuation, thus extending duration of prophylaxis beyond 100 days could be beneficial.