Effectiveness of Letermovir for Cytomegalovirus Prophylaxis in Seropositive Allogeneic Hematopoietic STEM Cell Transplant Recipients: A Global Systematic Review
Author(s)
Sepassi A1, Saunders I2, Bounthavong M3, Watanabe J1
1University of California, Irvine School of Pharmacy & Pharmaceutical Sciences, Irvine, CA, USA, 2University of California, San Diego, Los Angeles, CA, USA, 3University of California-San Diego, San Diego, CA, USA
Objectives: Cytomegalovirus (CMV) is associated with mortality in up to 30% of seropositive allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Letermovir (LET) was approved in 2017 for CMV prophylaxis. However, the literature evaluating the effectiveness of LET compared to traditional pre-emptive therapy (PET) is limited. This review aimed to summarize the effectiveness of LET compared to PET across the globe. Methods: A systematic literature search of CMV studies between 2011 and 2021using PubMed, Scopus, and ClinicalTrials.gov databases was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Outcomes studied included clinically significant CMV infection incidence (CS-CMVi), CMV disease, acute graft-versus-host-disease (GVHD), and all-cause mortality with LET compared to PET. Results: After inclusion and exclusion criteria were applied, fourteen studies were included in the analysis (one randomized clinical trial and thirteen retrospective observational cohort studies). All studies used prophylactic LET up to day +100 post-transplant, with various outcome follow-up periods ranging from day +100 to day +300. Incidence rates of CS-CMVi ranged from 4%-48.8% for LET and 41%-82.7% for PET. Rates of CMV disease ranged from 0%-3.8% for LET and 2%-9.6% with PET. GVHD rates ranged from 2%-47.6% with LET and 30%-50% with PET. PCR cutoffs used to define CS-CMVi ranged from 135 IU/mL to 3200 IU/mL. All-cause mortality ranged from 7.9%-15.4% with LET and 8.1%-42% with PET. Conclusions: Current published studies on the use of LET vs PET for CMV prophylaxis in allo-HCT patients varied considerably in terms of follow-up periods studied and PCR thresholds applied to define CS-CMVi, limiting precise evaluation of LET effectiveness. However, ranges in all outcomes for LET demonstrated consistent improvement than ranges resulting in PET use, suggesting a trend in LET effectiveness over PET. Guidelines must focus on more standardized recommendations to facilitate the effectiveness of future studies.
Conference/Value in Health Info
2022-05, ISPOR 2022, Washington, DC, USA
Value in Health, Volume 25, Issue 6, S1 (June 2022)
Code
CO97
Topic
Clinical Outcomes, Study Approaches
Topic Subcategory
Clinical Outcomes Assessment, Literature Review & Synthesis
Disease
Drugs, Infectious Disease (non-vaccine)