580 - Refractory and Resistant CMV Infections in Hematopoietic Cell Transplant Recipients in the Letermovir Primary Prophylaxis Era

Background: CMV reactivation is one of the most common infections after allogeneic hematopoietic cell transplantation (allo-HCT) and carries considerable morbidity and mortality. Primary prophylaxis with letermovir demonstrated in clinical trials reduction of the incidence of clinically significant CMV infection (CS-CMVi). This study aims at exploring the effect of letermovir primary prophylaxis on the occurrence of refractory or resistant CMV infections.

Methods: This is a single-center, retrospective cohort study of 537 consecutive allo-HCT CMV-seropositive recipients cared for between March 2016 and December 2018. Baseline demographics, transplant characteristics, CMV infections, treatment and mortality data were collected from the electronic medical record (Table 1). CMV outcomes were defined according to the standardized definitions for clinical trials. Data was analyzed on IBM® SPSS version 24 using a logistic regression model for multivariate analysis.

Results: Out of 537 patients identified, 123 received letermovir for primary prophylaxis during the first 100 days post-HCT and 414 did not. In a multivariate analysis, primary prophylaxis with letermovir was associated with a reduction in CS-CMVi (OR 0.11, 95% CI 0.06-0.20), CMV disease (OR 0.20, 95% CI 0.08-0.46) and refractory or resistant CMV infection (OR 0.11, 95% CI 0.02-0.49) (Table 2). Notably, there was no resistant CMV and no CMV-related mortality in the letermovir group. There was a trend towards lower all-cause mortality at day 100 in the letermovir group (OR 0.48, 95% CI 0.18-1.2).Table 1 - Baseline Characteristics.
Table 2 - Multivariate Analysis of Clinical Outcomes.


Conclusion: Our study showed a strong association between primary prophylaxis with letermovir and reduction in refractory or resistant CMV infections and CMV disease in allo-HCT recipients.