Letermovir does not affect long-term polyclonal immune reconstitution after allogeneic hematopoietic stem cell...

Letermovir (LET) is an effective prophylaxis for human cytomegalovirus (HCMV) reactivations in HCMV-seropositive patients after allogeneic stem cell transplantation (allo-SCT). HCMV promotes polyfunctional T-cell responses, leading to HCMV-specific immune reconstitution (IR), thus contributing to polyclonal IR.

We retrospectively analyzed HCMV-seropositive patients undergoing allo-SCT with ATG-based GvHD prophylaxis to assess the impact of LET on timing and quality of polyclonal IR. Two cohorts were identified: a pre-emptive treatment (PET) historical cohort transplanted without LET prophylaxis and a LET cohort receiving LET until at least day +100. All patients underwent weekly HCMV-DNA monitoring during the first 100 days post-allo-SCT. Immune monitoring was performed by flow cytometry, quantifying CD3+CD4+, CD3+CD8+ T-cells, CD19+ B-cells, and CD56+CD16+ NK-cells monthly during the first year after transplantation.

A total of 276 HCMV-seropositive patients were analyzed, 99 (36%) in the LET cohort and 177 (64%) in the PET cohort. LET significantly reduced the incidence of clinically significant HCMV infections during the first 100 days [28.3% in the LET cohort vs. 68.4% in the PET cohort (p<0.001)]. The cumulative incidence of IR 18 months after allo-SCT was comparable in the two groups [24% in the LET cohort vs. 27% in the PET cohort (p=0.393)]. These data were supported by multivariable analysis (HR 1.2, 95% CI 0.74-1.95, p = 0.463). Distinct immune dynamics were observed in the LET cohort, including lower early CD8+ T-cell counts and earlier NK-cell expansion peak.

Despite these differences, LET does not appear to influence the long-term incidence and composition of IR.