Work

75: Prevention of Late CMV Disease After HCT: A Randomized Double-Blind Multicenter Trial of Valganciclovir (VGCV) Prophylaxis Versus PCR-guided GCV/VGCV Preemptive Therapy

Year: 2008

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: Background: Late CMV disease is an important complication after allogeneic HCT. PCR surveillance followed by preemptive therapy (PET) is costly and often not feasible. VGCV prophylaxis may prevent late CMV-related complications. Methods: Between day 80 and day 120 after HCT, CMV seropositive or D+/R- allograft recipients with CMV infection prior to day 80 or GVHD were randomized to receive VGCV prophylaxis (900 mg/day) or placebo (Plac) until day 270. Patients were monitored weekly for CMV DNA by plasma PCR, blood chemistry and CBC/differential. IV GCV (5 mg/kg twice daily) or VGCV (900 mg/kg twice daily) was given if CMV DNA was > 1000 copies/mL. The primary endpoint was a composite of CMV disease or invasive bacterial/fungal infection or death by day 270 and the study was designed to show superiority of VGCV prophylaxis. Follow-up was until day 640 after HCT. Neutropenia was analyzed while receiving study drug and by day 270. All analyses were by intent-to-treat. Results: 184 patients were randomized. All patients completed follow-up through day 270; 84% (VGCV) and 82% (Plac) completed follow-up through day 640 (as of 9/30/2007). There was no observed difference between the groups in the primary endpoint at day 270 (VGCV: 20%, Plac: 21%, hazard ratio [HR] 1.0, 95% CI 0.5–1.9, P = 0.96) and 640 (39% and 40%, HR 0.9, 95% CI 0.6–1.5, P = 0.8). Valganciclovir prophylaxis reduced CMV PCR positivity (11% and 36%, HR 0.3, 95% 01.-0.5, P = 0.0002). There was a trend towards more neutropenia on double-blind study drug (absolute neutrophil count [ANC] < 1000/mm3 43% and 29%, HR 1.7, 95% CI 0.9–2.9, P = 0.08) but no significant difference was observed at day 270 (HR 1.3, 95% CI 0.8–2.1, p = 0.21 for ANC < 1000/mm3). The number and severity of adverse events AEs (including SAEs) was similar between the groups. There was also no significant difference in secondary endpoints, including CMV disease at day 270 (2% in both groups, HR 0.9, 95% CI 0.1–6.5) and 640 (6% and 5%, HR 1.2, 95% CI 0.3–4.5), HSV/VZV infections by day 640, death at any time, or relapse of the underlying disease. Conclusion: VGCV prophylaxis was not superior in reducing the composite endpoint of CMV disease, invasive bacterial or fungal infection or death. The incidence of CMV disease was low in both groups. VGCV reduced CMV DNAemia and the need for PET. The rate of neutropenia and other AEs was high but not significantly different between the groups. The study was not designed to test for equivalency.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2007.12.083