Prophylaxis Against Cytomegalovirus Infections with Oral Maribavir in Allogeneic Stem Cell Transplant Recipients: Results of a Randomized, Double-Blind, Placebo-Controlled Trial.

Cytomegalovirus (CMV) remains a major threat to recipients of allogeneic stem cell transplants (SCT). Potential toxicities of currently available anti-CMV agents complicate their use in this population. Maribavir (MBV) is an oral antiviral drug with a unique mechanism of action against CMV and a promising safety profile in early clinical studies. This randomized, double-blind, multicenter, dose-ranging study enrolled adult CMV-seropositive recipients of allogeneic SCT. After engraftment, patients were randomized to receive CMV prophylaxis with placebo or MBV at one of three doses for up to 12 weeks. CMV surveillance was performed weekly with both CMV pp65 antigenemia and plasma CMV DNA PCR assays. If CMV was detected, study drug was stopped and preemptive anti-CMV therapy started as per standard practice at each center. A total of 111 patients were enrolled (median age 47 years; 70% myeloablative SCT; 53% related donor). Incidence of CMV infection or disease in the first 100 days post-SCT are shown in the table. The safety profile of maribavir was favorable in this patient population; most adverse events occurred at similar rates in placebo and MBV groups. There was no adverse impact of MBV on neutrophil counts or other laboratory or ECG parameters. Consistent with prior clinical studies, the most notable events that appeared to be associated with MBV were mild-moderate taste disturbance, nausea, and diarrhea. In conclusion, maribavir prophylaxis reduced the rate of CMV infection compared to placebo, with a favorable safety profile in this complex patient population. Phase 3 studies of maribavir in stem cell and solid organ transplant recipients are being planned.