Letermovir prophylaxis guided by cytomegalovirus cell-mediated immunity improves the outcomes of allogeneic hematopoietic stem cell transplant recipients

Abstract Background The control of cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) depends heavily on the reconstitution of CMV-specific cell-mediated immunity (CMI). This study aimed to assess whether CMV-CMI-guided letermovir prophylaxis is more effective than a fixed-duration approach in reducing the incidence of late-onset clinically significant CMV infection (cs-CMVi). Methods This retrospective study included 182 adults who underwent allo-HSCT at four participating hospitals. Individuals who received transplantation between June 2022 and April 2023 were treated with a fixed 100-day course of letermovir (fixed-duration group, n = 78), while those transplanted from February 2023 to February 2024 received letermovir based on their CMV-CMI status (CMV-CMI-guided group, n = 104). Results The 1-year cumulative incidence of late-onset cs-CMVi was significantly lower in the CMV-CMI-guided group compared with the fixed-duration group (9.7% vs. 24.8%, p = 0.019). The CMV-CMI-guided group also had improved overall survival (89.1% vs. 77.1%, p = 0.04) and relapse-free survival (88.4% vs. 76.8%, p = 0.01). Patients were divided into high-risk (HR, n = 36) and low-risk (LR, n = 146) groups, based on risk factors for late-onset cs-CMVi. Among HR individuals, the cumulative incidence of late-onset cs-CMVi was significantly lower in the CMV-CMI-guided group than in the fixed-duration group (12.5% vs. 46.3%, p = 0.04). Conclusions CMV-CMI-guided letermovir prophylaxis may help reduce the risk of late-onset cs-CMVi, particularly in individuals at high risk.