Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study

Abstract

The anti-cytomegalovirus (CMV) activity and safety of oral maribavir in CMV-seropositive allogeneic stem-cell transplant recipients were evaluated in a randomized, double-blind, placebo-controlled, dose-ranging study. After engraftment, 111 patients were randomized to receive CMV prophylaxis with maribavir (100 mg twice daily, 400 mg once daily, or 400 mg twice daily) or placebo. Within the first 100 days after transplantation, the incidence of CMV infection based on CMV pp65 antigenemia was lower in each of the respective maribavir groups (15%, P = .046; 19%, P = .116; 15%, P = .053) compared with placebo (39%). Similarly, the incidence of CMV infection based on plasma CMV DNA was lower in each of the respective maribavir groups (7%, P = .001; 11%, P = .007; 19%, P = .038) compared with placebo (46%). Anti-CMV therapy was also used less often in patients receiving each respective dose of maribavir (15%, P = .001; 30%, P = .051; 15%, P = .002) compared with placebo (57%). There were 3 cases of CMV disease in placebo patients but none in the maribavir patients. Adverse events, mostly taste disturbance, nausea, and vomiting, were more frequent with maribavir. Maribavir had no adverse effect on neutrophil or platelet counts. These results show that maribavir can reduce the incidence of CMV infection and, unlike ganciclovir, does not cause myelosuppression.

Trial registration: ClinicalTrials.gov NCT00223925.

Figures

Figure 1

Mean plasma concentration-time profiles of maribavir. Blood samples were taken up to 8 hours after dose. Symbols represent maribavir dose groups: 100 mg twice daily (●), 400 mg once daily (■), and 400 mg twice daily (▴). (A) Plasma concentration-time profile on day 7. The 100-mg twice-daily, 400-mg once-daily, and 400-mg twice-daily groups comprised 17, 11, and 10 patients, respectively. (B) Plasma concentration-time profile at week 4. The 100-mg twice-daily, 400-mg once-daily, and 400-mg twice-daily groups comprised 12, 9, and 3 patients, respectively.

Figure 2

Incidence of CMV infection or disease. Kaplan-Meier curves of the cumulative incidence of CMV infection (as detected by either a positive pp65 antigenemia or positive plasma CMV DNA PCR assay, from either the central laboratory or local laboratory testing) or CMV disease in placebo and maribavir groups. P values vs placebo determined by Cox proportional hazards regression model. Symbols represent treatment groups: placebo (♦), 100 mg twice daily (●), 400 mg once daily (■), and 400 mg twice daily (▴).