Clinical burden of late-onset, clinically significant CMV infection beyond 100 days in allo-HSCT patients after letermovir prophylaxis.

Abstract

Objective: Letermovir (LET) is effective for preventing cytomegalovirus infection (CMVi) and CMV disease in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, clinically significant (cs)-CMVi can occur after LET cessation. We retrospectively evaluated the clinical burden of late-onset cs-CMVi in patients who had received LET following allo-HSCT in Japan.

Methods: The Japan Medical Data Center health insurance claims database was interrogated for adult patients who had received LET ≤100 days after allo-HSCT (May 28, 2018, to December 31, 2022). Cohorts 1 and 2 (primary analyses) comprised cs-CMVi-positive and -negative patients, respectively, followed for ≥180 days after the first cs-CMVi-related claim; Cohorts 3 and 4 (exploratory analysis) included patients meeting Cohort 1 or 2 criteria, respectively, but without follow-up duration limitation.

Results: Data for 155 patients (Cohort 1, n = 47; Cohort 2, n = 108) were analyzed. cs-CMVi rates were higher in patients at high (n = 72) versus low risk (n = 83) of CMVi (43.4% vs 15.3%; p = 0.0003), with no difference in frequency of CMV disease. In Cohort 1, median time from 100 days post-transplantation to first cs-CMVi was 35.0 days. Rates of hospital admissions were higher in Cohort 1 versus Cohort 2 (p = 0.0061), and mean duration of anti-CMV drug prescription was longer in high- versus low-risk patients (p = 0.0024). New-onset graft-versus-host disease occurred ≥101 days post-transplantation in three patients (all Cohort 1).

Conclusion: This study demonstrates the great burden of late-onset cs-CMVi in patients after allo-HSCT. Extended LET prophylaxis beyond 100 days post-transplant may benefit especially those at high risk of cs-CMVi.