Efficacy and Safety of Primary Letermovir Prophylaxis for Cytomegalovirus Infection in Pediatric Patients Undergoing Allogeneic Transplantation: A Single-Centre, Retrospective, Real-World Analysis

Background: Cytomegalovirus (CMV) infection is a common and life-threatening complication following allogeneic haematopoietic stem cell transplantation (allo-HSCT) and patients receiving alternative donor transplantation were at high risk for CMV infection. Letermovir (LET) has been the standard prophylaxis for adult recipients, but published studies in children remain limited, especially for recipients of haploidentical donor (HID) or unrelated cord blood (UCB).

Methods: We retrospectively analyzed children with or without LET prophylaxis, who underwent HID or UCB transplantation between January 2021 and December 2023, to evaluate the efficacy and safety of LET for clinically significant CMV infection (csCMVi) up to 180 days after allo-HSCT. Additionally, we analyzed the influence of donor type on the efficacy of LET.

Results: Of the 151 consecutive patients, 67 received LET, including 35 HID recipients and 32 UCB recipients. They were given 120/240 mg of LET daily, with an average start time of day +13 (1-44) after transplantation, and continued until day +100 after transplantation. During the 180 days after transplantation, we found that the LET group had a lower incidence of csCMVi than the non-LET group (13.4% vs. 56.0%, P＜0.001). Among patients with csCMVi, the LET group had a later mean time of infection onset (day +71 vs. day +41, P=0.306), a lower mean CMV DNA peak load (343 IU/ml vs. 1080 IU/ml, P=0.015) and a shorter mean duration (11 days vs. 19 days, P=0.113) than the non-LET group. Furthermore, in the LET group, later administration of LET was identified as a risk factor for the occurrence of csCMVi (hazard ratio: 1.08, 95% CI: 1.01 - 1.16, P=0.020). Regarding donor type, we found that the HID subgroup had a lower incidence of csCMVi during follow-up than the UCB subgroup (1/35 2.9% vs. 8/32 25.0%, P=0.009). In terms of safety, the incidence and severity of adverse events, leukaemia relapse and overall survival were similar between the two groups.

Conclusion: LET is effective and safe in preventing CMV reactivation among Chinese children undergoing alternative donor transplantation, especially in HID recipients.

No relevant conflicts of interest to declare.

Letermovir is a novel exclusive anti-CMV drug that has been recommended as the standard prophylaxis for adult seropositive recipients following allogeneic hematopoietic stem cell transplantation by the US Food and Drug Administration (FDA).