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 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 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.