Real-world use of letermovir for CMV prevention in allogeneic hematopoietic cell transplantation recipients in France: a national claims database study

Background Letermovir is the only drug indicated for the prophylaxis of cytomegalovirus (CMV) reactivation in CMV-positive allogeneic hematopoietic cell transplantation (HCT) recipients. It is recommended that letermovir be started on the day of HCT and no later than 28 days post-HCT, usually around the fifth day, and continued for 100 days post-HCT and potentially beyond. Due to its recent availability, real-world data on letermovir prophylactic use are scarce, with recent studies advocating for an extension of its duration from 100 to 200 days. Objectives This study aimed to describe i) patients with letermovir prophylaxis in France and ii) letermovir prophylaxis modalities and clinical events. Study design This is a non-interventional retrospective cohort study based on claims data from the French National Health Data System (SNDS), which gathers all reimbursed inpatient and outpatient healthcare consumptions of French residents. Data on patients with letermovir prophylaxis (code J05AX18) between 1 March 2020 (when letermovir became available in France) and 31 December 2021 (the latest year of data available at the time of access) were extracted. Among them, patients with allogeneic HCT presenting ≥6 months of follow-up after letermovir initiation (6M-HCT+) were followed until the end of the study or death to describe the prophylaxis modalities. Finally, among the 6M-HCT+ patients, those with a complete course of letermovir (i.e., letermovir discontinuation formally identified before the end of follow-up) were identified to describe the letermovir courses and clinical events. Results Among the 1,706 patients identified, 1,649 were included in the study population. Of these, data from 511 (31.0%) 6M-HCT+ patients and 304 (18.4%) with a complete first letermovir course were extracted. The median age at letermovir initiation was 57.0 years. The mean (SD) prophylaxis duration was 152.0 (96.4) days. The majority (65.2%, n = 195) of the patients presented with a single course, with a mean (SD) duration of 180.1 (94.9) days. Among the 109 patients (35.8%) who received a second course, the mean (SD) durations of the first and second courses were 101.7 (77.1) and 103.2 (81.8) days, respectively, for a total exposure of 204.9 (154.3) days. Conclusions The mean duration of a letermovir course among 6M-HCT+ patients was 152 days. More than 30% of the patients received a second course, while having a shorter first course than those who were treated only once. Longer initial letermovir exposure may be associated with a decrease in subsequent need for letermovir exposure.