Letermovir for cytomegalovirus prophylaxis after allogeneic hematopoietic stem cell transplantation in acute leukemia patients: results of the LETreal study.

OBJECTIVE: Cytomegalovirus (CMV) infection can cause severe morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Letermovir is recommended as CMV prophylaxis for allo-HSCT recipients. This study aimed to further confirm the efficacy of letermovir prophylaxis in different subgroups based on a large cohort of acute leukemia patients following allo-HSCT. METHODS: 1331 acute leukemia patients who underwent allo-HSCT (including 978 and 353 patients with and without letermovir prophylaxis, respectively) were enrolled. The occurrence of clinically significant CMV infection (cs-CMVi), CMV disease, and refractory CMV infection were evaluated. Propensity score matching (PSM) was applied to balance baseline characteristics between patients with and without letermovir. RESULTS: In patients receiving letermovir, the 100-day cumulative incidence of cs-CMVi after allo-HSCT was 7.1% (95% CI, 5.5-8.7%), and this rate was greater in children; however, no variables increased the risk of cs-CMVi at 100 days according to multivariate analysis. The cumulative incidence rates of cs-CMVi and CMV disease between 100 and 200 days after allo-HSCT for patients receiving letermovir prophylaxis were 12.5% (95% CI, 10.3-14.7%) and 1.6% (95% CI, 0.8-2.4%), respectively. For the subgroup of patients who did not experience a CMV infection within the first 100 days, these rates were 11.7% (95% CI, 9.5-13.9%) and 1.4% (95% CI, 0.6-2.2%), respectively. Donor-/recipient+ CMV serostatus (44.2%, HR, 5.00; P<0.001) independently increased the risk of cs-CMVi, and age > 60 years (5.0%, HR, 4.01; P = 0.030) increased the risk of CMV disease between 100 and 200 days after allo-HSCT. After PSM adjustment, letermovir prophylaxis was associated with a lower incidence of cs-CMV infection (grade II-IV: 1.9% vs. 10.7%, P = 0.024; grade III-IV: 0% vs. 27.3%, P<0.001) in patients with acute graft-versus-host disease (GVHD). The incidence of cs-CMVi was 18.4% (95% CI, 7.4-29.4%) among chronic GVHD patients receiving letermovir prophylaxis. The incidence of cs-CMVi between 100 and 200 days after allo-HSCT was comparable between patients with prolonged letermovir prophylaxis and those without letermovir prophylaxis. CONCLUSION: We confirmed the efficacy of letermovir prophylaxis in different subgroups, but the subgroup who would benefit most from prolonged prophylaxis should be further clarified in the future.