Letermovir Primary and Secondary Prophylaxis in Pediatric Recipients of Allogeneic Haematopoietic Stem Cell Transplant.

Background: CMV reactivation represents one of the most frequent infectious complications post HSCT. Letermovir is a viral terminate inhibitor which has been approved in adults for the prophylaxis of post HSCT CMV reactivation. Its use in pediatric HSCT recipient was recently approved by US FDA but data on the use of letermovir in children remain limited.

Objective: We aimed at comparing the incidence of CMV reactivation in a more recent cohort of pediatric HSCT recipients receiving primary or secondary prohylaxis with letermovir with a previous cohort of children receiving no prophylaxis. We analyzed the risk factors for CMV reactivation among IgG seropositive recipients and the role of CMV reactivation on treatment related mortality/overall survival.

Methods: This is a single center retrospective study which enrolled all consecutive patients aged <21 years who underwent allogeneic HSCT between 1 January 1, 2014 and October 31, 2023 at the pediatric HSCT Unit of the Fondazione IRCCS San Gerardo dei Tintori in Monza

Results: 287 patients who received 308 HSCT were analyzed. Three months cumulative incidence of CMV reactivation was 29.5% (95% CI: 24.3-35) in the standard cohort versus 3.7% (95% CI: 0.3-16.3) in the cohort of patients receiving letermovir as primary prophylaxis (P = .0029). The use of letermovir as well as the use of a HLA-identical donor with no serotherapy, bone marrow as a source of stem cell and the absence of acute GVHD were statistically significant protective factors against CMV reactivation at multivariate analysis. At 3 months after discontinuation of preemptive therapy, the cumulative incidence of CMV reactivation was 0% for the 15 patients receiving letermovir as secondary prophylaxis versus 34.7% (SE 5.8, 95% CI: 23.7-46.0) for the 72 patients not receiving secondary prophylaxis.

Conclusions: Letermovir is safe and efficacious in preventing CMV reactivation in pediatric patients undergoing HSCT in both primary and secondary prophylaxis.