Decreased Incidence of CMV Infection with Letermovir Prophylaxis in Alternative Donor Allogeneic Hematopoietic-Cell Transplantation with Post-Transplant Cyclophosphamide, Real-Life Data from Argentina.

Introduction Post-transplant cyclophosphamide (PTCy) is an established platform for graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT). A study by CIBMTR demonstrated that it is associated with a higher incidence of cytomegalovirus infection (CMVi), regardless of the donor type. Primary prophylaxis (PP) with letermovir (L) has shown benefits in reducing the rate of CMVi. Objectives Primary: To evaluate the cumulative incidence (CI) of CMVi post allo-HCT in patients who used PTCy. Secondary: To assess the median time to engraftment, the CI of acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse (CIR), non-relapse mortality (NRM), and overall survival (OS). Materials and Methods Retrospective multicenter cohort study that included patients >18 years old with CMV positive serostatus from 5 GATMO-TC centers in Argentina who underwent allo-HCT between 1/2018 and 12/2022 and received PTCy. Patients who received PP with L were compared to those that did not receive L. CMVi was defined as positive viremia requiring treatment and/or organ damage due to CMV. CI was used to calculate CMVi, GVHD, relapse, and NRM. Results A total of 136 patients were analyzed, 36 received PP with L. The median age at allo-HCT was 47.5 years, 62.5% were male, and the most frequent diagnoses were acute myeloid leukemia (52%) and acute lymphoblastic leukemia (36%). The majority underwent haploidentical allo-HCT (82.4%) and had myeloablative conditioning (61.8%). In the bivariate analysis between groups, there were no significant differences in age, sex, underlying disease, DRI, HCT-CI, donor type, conditioning intensity, source, and aGVHD ≥ grade 2. Differences were observed regarding disease status, with a higher number of intermediate-risk patients in the L group (p=0.022) and CMV serostatus, with more R+/D- patients in the L group (p=0.029). The median follow-up was shorter for the L group, 7.6 months (range: 0.4-29.6) vs. 13.2 months (range: 0.2-65.8). The CI of CMVi at day +100 was significantly lower in patients with L: 14% (CI 5-27) vs. 56% (CI 46-65), p=0.0003, and this benefit persisted at 1 year: 37% (CI 21-53) vs. 56% (CI 46-65), p=0.0019; Figure 1. Five patients developed CMVi during L, 4 with viremia and 1 with organ damage. The median time to engraftment, 100 and 180-days CI of grade 2-4 and 3-4 aGVHD, as well as 1 year CI of cGVHD and moderate/severe cGVHD, were comparable between both groups. There were no differences in relapse, NRM, and 1-year OS; Table 1. Conclusions Our experience is consistent with the data reported in the literature. It confirms the efficacy of L during the first 100 days of allo-HCT for CMV prevention in a high-risk cohort. In our country, access to the PP strategy is severely limited due to lack of coverage. It would be interesting to have a pharmacoeconomic study to demonstrate the advantages of L in terms of cost-effectiveness.