Effectiveness of letermovir for cytomegalovirus prophylaxis in allogeneic hematopoietic stem cell transplant recipients: A global systematic review

Objective(s): Letermovir (LET), a novel antiviral, has largely supplanted more traditional pre-emptive therapy (PET) for cytomegalovirus (CMV) prophylaxis in allogeneic hematopoietic stem cell transplant (allo-HCT) patients. Use of LET demonstrated efficacy against placebo in phase III randomized controlled trials, but is considerably more expensive than PET. This review aimed to evaluate the real-world effectiveness of LET in preventing clinically significant CMV infection (csCMVi) for allo-HCT recipients and related outcomes.Design: A systematic literature review was performed using an a priori protocol using PubMed, Scopus, and ClinicalTrials.gov from January 2010 to October 2021.Setting and Participants: Studies were included if they met the following criteria: LET compared with PET, CMV-related outcomes, patients aged 18 years or older, and English language-only articles. Descriptive statistics were used to summarize study characteristics and outcomes.Outcome Measures: CMV viremia, csCMVi, CMV end-organ disease, graft-versus-host-disease, all-cause mortality.Results: A total of 233 abstracts were screened, with 30 included in this review. Randomized trials demonstrated efficacy of LET prophylaxis in preventing csCMVi. Observational studies demonstrated varying degrees of effectiveness of LET prophylaxis compared with use of PET alone. All studies with a comparator group resulted in lower rates of csCMVi for patients using LET. Included studies varied widely by CMV viral load threshold cutoff and CMV test units, limiting synthesis of results owing to high heterogeneity.Conclusion: LET reduces risk of csCMVi, but lack of standardized clinical definitions on how to evaluate csCMVi and related outcomes largely prevent synthesis of results. Clinicians must consider this limitation in the context of evaluating the effectiveness of LET to other antiviral therapies, especially for patients at risk of late-onset CMV. Future studies should focus on prospective data collection through registries and concordance of diagnostic definitions to mitigate study heterogeneity.& COPY; 2023 American Pharmacists Association & REG;. Published by Elsevier Inc. All rights reserved.