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Letermovir Prophylaxis in Cytomegalovirus Seronegative Recipients with a Seropositive Donor Allogeneic Hematopoietic Cell Transplant: A Single-Center Experience

Year: 2025

Type: article

Abstract: Introduction Cytomegalovirus (CMV) reactivation is one of the most common viral infectious complications after allogeneic hematopoietic cell transplant (HCT). Letermovir (LTV) is effective at reducing clinically significant CMV infection (CS-CMVi) in CMV-seropositive patients, including among those with risk factors such as post-transplant cyclophosphamide (PTCy). CMV-seronegative recipients (R-) with a CMV-seropositive donor (D+) have a 20-30% risk of CMV infection but have been excluded from LTV clinical trials . The effectiveness of LTV prophylaxis in CMV D+/R- HCT remains unknown. Objectives The purpose of this study was to compare the cumulative incidence (CI) of CS-CMVi in CMV D+/R- adult HCT patients who did or did not receive LTV prophylaxis. Methods This was a single-center, retrospective, cohort study to compare the efficacy of LTV primary prophylaxis vs no prophylaxis (control group) for the prevention of CS-CMVi among CMV D+/R- adult HCT patients. Patients who received any CMV prophylaxis other than LTV were excluded. The primary outcome was CI of CS-CMVi, defined as CMV disease or CMV viremia requiring preemptive therapy. Secondary outcomes included the incidence of CS-CMVi at 100 and 200 days post-transplant, incidence of CMV viremia , and overall survival (OS). The CI of CS-CMVi and OS were evaluated using the Kaplan-Meier method, and Cox proportional hazards models were used to assess the association between outcome and use of LTV. Results A total of 126 patients were included, with 102 patients in the control group and 24 patients in the LTV group. Baseline characteristics were similar, except for more ATG use in the control group (25% vs 4%, p = 0.026; Table 1). In the LTV group, the median duration of LTV prophylaxis was 160 days (range 16 to 513 days). The CI of CS-CMVi was similar between groups (hazard ratio [HR] 0.879, 95% confidence interval [CI] 0.252-3.061, p = 0.839; Figure 1). The median time to CS-CMVi was shorter in the control group (56 days vs 263 days) with a similar median peak CMV DNA level (1130 IU/mL vs 900 IU/mL, p = 0.620). The incidence of CS-CMVi and CMV viremia was numerically higher among the control group at 100 days (CS-CMVi 12% vs 4%, p = 0.460 and CMV viremia 19% vs 4%, p = 0.119) and 200 days (CS-CMVi 13% vs 4%, p = 0.304 and CMV viremia 20% vs 4%, p = 0.075). The rate of CS-CMVi was similar among patients who received PTCy (n = 6, 15%) vs other GVHD prophylaxis (n = 12, 14%). Immunosuppression at the time of CS-CMVi included tacrolimus (n = 15, 83%), prednisone (n = 12, 67%), and ruxolitinib (n = 2, 11%). OS was not significantly different between the two groups (median 92 months vs not reached; HR 0.951, 95% CI 0.423-2.140; p = 0.903). Conclusion This study did not find a significant reduction in CS-CMVi among D+/R- HCT patients who received LTV but is limited by a small sample size. Prospective studies are needed to determine if D+/R- HCT patients benefit from primary prophylaxis with LTV.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.01.214