Letermovir prophylaxis and cytomegalovirus reactivation in adult allogeneic hematopoietic cell transplant recipients with graft versus host disease.

Abstract

7004 Background: Cytomegalovirus (CMV) is the most common clinically significant infection after allogeneic hematopoietic-cell transplantation (allo-HCT) and is associated with increased mortality. The risk for CMV reactivation increases with HLA mismatch, high dose corticosteroids, and graft versus host disease (GVHD). GVHD contributes to significant morbidity and mortality and is treated with immunosuppressive therapies that further increase CMV infection risk. In a phase III trial, letermovir prophylaxis had a lower incidence of CMV infection post-allo-HCT in patients at high risk of CMV reactivation when compared to placebo when given up to day +100. There is a lack of data concerning the effectiveness of letermovir in patients who develop GVHD and may continue letermovir past day +100. Methods: This was a single-center, retrospective study conducted at The Ohio State University. Demographics and transplant details were collected from medical records. The primary outcome was incidence of clinically significant CMV infection (CS-CMVi) within 200 days of allo-HCT. Secondary outcomes included incidence of CMV viremia, duration of letermovir therapy, mortality, and risk factors for CS-CMVi. Early death without CMV was treated as a competing risk for CS-CMVi, while relapse was a competing risk for non-relapse mortality (NRM). Proportional subdistribution or Cox hazards models were used to evaluate the association between use of letermovir and risk of CS-CMVi, NRM, or overall survival (OS) adjusting for potential confounding factors, where use of letermovir and GVHD were treated as time-dependent variables. Results: A total of 262 CMV-seropositive patients who received an allo-HCT between June 1, 2016 and June 30, 2020 were included. Of these, 119 patients received letermovir prophylaxis. A total of 111 patients received treatment for CS-CMVi, which included 82 of 143 (57%) who did not receive letermovir compared to 29 of 119 (24%) who received letermovir. Incidence of CMV viremia was significantly reduced with the use of letermovir in all patients (HR 0.21, 95% CI 0.12–0.34, p < 0.001) and among patients with acute GVHD grade >2 within 200 days post-allo-HCT (HR 0.12, 95% CI 0.05–0.32, p < 0.001), adjusting for age, gender, GVHD prophylaxis and use of ATG or T-cell depleted graft. The median duration of letermovir therapy was 97 days. Nine patients were continued on letermovir indefinitely for recurrent CMV viremia. Patients who received letermovir had decreased NRM (HR 0.41, 95% CI 0.18-0.96, p = 0.04) and improved OS (HR 0.46, 95% CI 0.23-0.95, p = 0.04). Conclusions: Letermovir prophylaxis significantly decreased CS-CMVi and improved NRM and OS in this real-world analysis. In addition, patients with acute GVHD had significantly less CMV viremia, suggesting potential benefit in continuing letermovir prophylaxis in this patient population.