Risk Stratification for Late‐Onset CMV Infection Following Prophylaxis With Letermovir in Allogeneic Stem Cell Transplant Recipients: Unraveling the Potential Role of CMV‐Specific Cell‐Mediated Immunity

Background Late‐onset CMV infection occurring after cessation of prophylaxis with letermovir (LTV) has been reported in a consistent number of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Objective The aim of this study was to investigate whether transplant characteristics and functional assays might be helpful to identify which patients might benefit from extending LTV prophylaxis to 200 days post‐HSCT. Study Design A total of 95 patients with hematological malignancies who received prophylaxis with LTV until Day +100 were included in the study. Analysis of CMV‐specific cell‐mediated immunity (CMV‐CMI) was performed with QuantiFERON‐CMV (QTF‐CMV) assay at the end of LTV administration. Results Overall, 23 patients experienced clinically significant CMV infection (csCMVi) after the end of prophylaxis with LTV, leading to a 20% cumulative incidence (CI) of csCMVi at 180 days. Seven of the 46 patients (15%) with positive QTF‐CMV at Day +100 had late‐onset csCMVi, compared to 15 of the 43 patients (35%) with negative QTF‐CMV ( p = 0.048). The CI of late‐onset csCMVi was 41.4% in patients with GVHD and negative QTF‐CMV as compared to 0% in patients with no GVHD and a positive QTF‐CMV ( p = 0.002). In multivariate analysis, D−/R+ CMV serology (OR 3.69:1.31–10.42, p = 0.014) and GVHD (OR 3.42: 1.00–11.66, p = 0.050) were factors independently associated with the probability of late‐onset csCMVi. Conclusion Our findings suggest that D−/R+ CMV serology and the presence of GVHD, combined with CMV‐QTF, may be considered as a useful tool to predict which patients receiving LTV might benefit from an extension of prophylaxis up to 200 days after HSCT.