Assessment of CMV infection in allo-HSCT recipients undergoing LMV prophylaxis by using an implemented diagnostic protocol to identify active viral replication

Letermovir (LMV), a novel antiviral agent targeting the cytomegalovirus (CMV) terminase complex, has significantly changed the management of adult allogenic hematopoietic stem cell transplant (allo-HSCT) recipients. In this retrospective, single-center study, we assessed our real-life experience in using an implemented diagnostic protocol to identify patients needing pre-emptive therapy (PET) or at high risk of developing CMV-related disease. The study included allo-HSCT recipients who received LMV prophylaxis (LMV group), compared with a historical control group of CMV seropositive patients undergoing allo-HSCT. These patients were managed using a pre-emptive strategy. Both study groups were followed from the day of transplant for up to 200 days. Among the 110 patients receiving LMV prophylaxis, CMV DNAemia was detected in 43 cases (39.1%). However, infectious virions associated with active CMV infection were identified only in four patients (4/43, 9.3%), who required the interruption of LMV and the initiation of PET (CS-CMVi cases). We evaluated the incidence of CS-CMVi at 100 and 200 days post-transplant, comparing patients undergoing LMV prophylaxis with a historical group managed by PET. At 100 days post-transplant, the cumulative incidence of CS-CMVi was significantly lower in the LMV group compared to the control group (3.6% versus 39.1%; p < 0.001). The same result was observed at 200 days post-transplant. These findings confirm that LMV has significantly decreased the incidence of CS-CMVi in CMV seropositive patients and underline the clinical utility of an implemented diagnostic protocol including DNase or RNAemia tests to discriminate between active and abortive CMV infection.