Treatment for First Cytomegalovirus Infection Post-Hematopoietic Cell Transplant in the AURORA Trial: A Multicenter, Double-Blind, Randomized, Phase 3 Trial Comparing Maribavir With Valganciclovir.
Clin Infect Dis
; 78(3): 562-572, 2024 03 20.
Article
en En
| MEDLINE
| ID: mdl-38036487
ABSTRACT
BACKGROUND:
Neutropenia may limit the use of valganciclovir treatment for cytomegalovirus (CMV) infection following hematopoietic cell transplant (HCT). A phase 2 study indicated efficacy of maribavir with fewer treatment-limiting toxicities than valganciclovir.METHODS:
In this multicenter, double-blind, phase 3 study, patients with first asymptomatic CMV infection post-HCT were stratified and randomized 11 to maribavir 400â mg twice daily or valganciclovir (dose-adjusted for renal clearance) for 8 weeks with 12 weeks of follow-up. The primary endpoint was confirmed CMV viremia clearance at week 8 (primary hypothesis of noninferiority margin of 7.0%). The key secondary endpoint was a composite of the primary endpoint with no findings of CMV tissue-invasive disease at week 8 through week 16. Treatment-emergent adverse events (TEAEs) were assessed.RESULTS:
Among patients treated (273 maribavir; 274 valganciclovir), the primary endpoint of noninferiority of maribavir was not met (maribavir, 69.6%; valganciclovir, 77.4%; adjusted difference -7.7%; 95% confidence interval [CI] -14.98, -.36; lower limit of 95% CI of treatment difference exceeded -7.0%). At week 16, 52.7% and 48.5% of patients treated (maribavir and valganciclovir, respectively) maintained CMV viremia clearance without tissue-invasive disease (adjusted difference 4.4%; 95% CI -3.91, 12.76). With maribavir (vs valganciclovir), fewer patients experienced neutropenia (16.1% and 52.9%) or discontinued due to TEAEs (27.8% and 41.2%). Discontinuations were mostly due to neutropenia (maribavir, 4.0%; valganciclovir, 17.5%).CONCLUSIONS:
Although noninferiority of maribavir to valganciclovir for the primary endpoint was not achieved based on the prespecified noninferiority margin, maribavir demonstrated comparable CMV viremia clearance during post-treatment follow-up, with fewer discontinuations due to neutropenia. Clinical Trials Registration. NCT02927067 [AURORA].Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Infecciones por Citomegalovirus
/
Trasplante de Células Madre Hematopoyéticas
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Diclororribofuranosil Benzoimidazol
/
Neutropenia
Límite:
Humans
Idioma:
En
Revista:
Clin Infect Dis
Asunto de la revista:
DOENCAS TRANSMISSIVEIS
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos