Letermovir Prophylaxis Guided by Cytomegalovirus Cell-Mediated Immunity Improves the Outcomes of Allogeneic Hematopoietic Stem Cell Transplant Recipients

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 (CMV-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 4 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 receiving transplantation 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 = .019). The CMV-CMI-guided group also had improved overall survival (89.1% vs 77.1%, P = .04) and relapse-free survival (88.4% vs 76.8%, P = .01). Patients were divided into high-risk (n = 36) and low-risk (n = 146) groups, based on risk factors for late-onset cs-CMVi. Among high-risk 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 = .04). CONCLUSIONS: CMV-CMI-guided letermovir prophylaxis may help reduce the risk of late-onset cs-CMVi, particularly in individuals at high risk. CLINICAL TRIALS REGISTRATION: NCT06708130.