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
Author:
Papanicolaou Genovefa A1, Avery Robin K2, Cordonnier Catherine3, Duarte Rafael F4, Haider Shariq5, Maertens Johan6, Peggs Karl S7, Solano Carlos8, Young Jo-Anne H9, Fournier Martha10ORCID, Murray Rose Ann10, Wu Jingyang10, Winston Drew J11, Singhal Deepak, Sasadeusz Joe, Maertans Johan, Georgala Aspasia, Selleslag Dominik, Verlinden Anke, Kerre Tessa, De Becker Ann, Haider Shariq, Wright Alissa, Wu Depei, Vrhovac Radovan, Cordonnier Catherine, Berceanu Ana, Francois Sylvie, Michonneau David, Huynh Anne, Bethge Wolfgang, Kaufmann Martin, Stelljes Matthias, Franke Georg-Nikolaus, Schmitt Timo, Müller Lutz, Ahlgrimm Manfred, Niederland Judith, Tsirigotis Panagiotis, Ram Ron, Shemtov Noga, Rosenvald-Zuckerman Tsila, Cutini Ilaria, Busca Alessandro, Onida Francesco, Tecchio Cristina, Browett Peter, Do Young Rok, Kim Sung Hyun, Ho Aloysius, Koh Liang Piu, Lopez Maria Lourdes Vazquez, Jimenez Javier Lopez, Coll Christelle Ferra, De la Camara Rafael, Solano Carlos, Mussetti Alberto, Llamas Juan Carlos Vallejo, Suñol Pere Barba, Chacón Manuel Jurado, Duarte Rafael F, Rodríguez María Aranzazu Bermúdez, Mueller Nicolas, Ozdogu Hakan, Gurman Gunhan, Bloor Adrian, Kishore Bhuvan, Peggs Kari S, Milojkovic Dragana, Orchard Kim, Toth Arpad Gabor, Koh Mickey, Avery Robin K, Pisano Jennifer, Alangaden George, Winston Drew J, Papanicolau Genovefa, Gewurz Benjamin, Marty Francisco M, Young Jo-Anne H, Hagen Patrick, Reshef Ran, Abedin Sameem, Shaughnessy Paul, Gibson Laura, Shore Joan Tsiporah, Bachier Carlos R, Yared Jean, Malinis Maricar,
Affiliation:
1. Memorial Sloan Kettering Cancer Center , New York, New York , USA 2. Johns Hopkins University , Baltimore, Maryland , USA 3. Henri Mondor Hôpital, Assistance Publique-Hopitaux de Paris, and Université Paris-Est-Créteil , Créteil , France 4. Hospital Universitario Puerta de Hierro Majadahonda , Madrid , Spain 5. Hamilton Health Sciences Corporation , Ontario , Canada 6. University Hospitals Leuven, KU Leuven , Leuven , Belgium 7. University College London Hospitals NHS Foundation Trust , London , United Kingdom 8. Hospital Clínico Universitario, University of Valencia , Valencia , Spain 9. University of Minnesota , Minneapolis, Minnesota , USA 10. Takeda Development Center Americas, Inc , Lexington, Massachusetts , USA 11. Los Angeles Medical Center, University of California , Los Angeles, California , USA
Abstract
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 1:1 to maribavir 400 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].
Funder
Takeda Development Center Americas, Inc Caudex
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Microbiology (medical)
Cited by
11 articles.
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