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Background: Lung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off-label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients., Methods: This retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post-LET initiation; secondary outcomes included hematologic changes., Results: A total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R-), with LET initiated a median of 9.6 months post-transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p = .370). The median (interquartile range) white blood cell (WBC) count was 3.1 (2.1-5.6) at LET initiation which increased to 5.1 (3.9-7.2) at the end of follow-up (p <.001). For VGCV controls, WBC was 4.8 (3.4-7.2) at baseline and 5.4 (3.6-7.2) at the end of follow-up; this difference was not statistically significant (p = .395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001)., Conclusion: LET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV., (© 2024 Wiley Periodicals LLC.)

Background: Cytomegalovirus (CMV) infection is extremely common after lung transplant and can be associated with significant morbidity and mortality. Current practice suggests the use of 900 mg daily of valganciclovir for CMV prophylaxis, but there is no literature assessing whether 450 mg daily of valganciclovir is sufficient in intermediate CMV risk lung transplant recipients. Therefore, we sought to assess the role of low-dose valganciclovir (LDV) versus high-dose valganciclovir (HDV) prophylaxis in intermediate-risk (R+) recipients. Methods: We conducted a retrospective analysis on lung transplant recipients at the Norton Thoracic Institute in Phoenix, Arizona looking at intermediate-risk patients that received either valganciclovir 450 mg per day (LDV) or 900 mg/day (HDV). All patients were followed for 1 year posttransplant for incidence of CMV viremia. The primary outcome was the rate of CMV viremia as determined by a positive CMV polymerase chain reaction ([PCR] >2.7 log copies/mL). Secondary outcomes included rate of adverse events, acute cellular rejection, and mortality. Results: The primary analysis included 103 patients (55 in the LDV group, 48 in the HDV group). In the LDV group, 9 patients (16.4%) developed CMV viremia compared to 4 (8.3%) in the HDV group (p=0.221) with no difference observed in adverse event rates between groups. Conclusion: There was no statistical difference between groups for the primary outcome. However, the effect size demonstrated in this analysis may be of clinical relevance and valganciclovir 450 mg daily would not be recommended in intermediate risk lung transplant recipients at this time. To confirm our results, further prospective studies enrolling larger patient populations are necessary. [ABSTRACT FROM AUTHOR]