First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab: final analysis of the randomized, phase III iLLUMINATE trial


Por: Moreno C., Greil R., Demirkan F., Tedeschi A., Anz B., Larratt L., Simkovic M., Novak J., Strugov V., Gill D., Gribben J.G., Kwei K., Dai S., Hsu E., Dean J.P., Flinn I.W.

Publicada: 1 ene 2022
Resumen:
iLLUMINATE is a randomized, open-label phase III study of ibrutinib plus obinutuzumab (n=113) versus chlorambucil plus obinutuzumab (n=116) as first-line therapy for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Eligible patients were aged =65 years, or <65 years with coexisting conditions. Patients received oral ibrutinib 420 mg once daily until disease progression or unacceptable toxicity or six cycles of oral chlorambucil, each in combination with six cycles of intravenous obinutuzumab. After a median follow-up of 45 months (range, 0.2-52), median progression-free survival continued to be significantly longer in the ibrutinib plus obinutuzumab arm than in the chlorambucil plus obinutuzumab arm (median not reached versus 22 months; hazard ratio=0.25; 95% confidence interval: 0.16-0.39; P<0.0001). The best overall rate of undetectable minimal residual disease (<0.01% by flow cytometry) remained higher with ibrutinib plus obinutuzumab (38%) than with chlorambucil plus obinutuzumab (25%). With a median treatment duration of 42 months, 13 months longer than the primary analysis, no new safety signals were identified for ibrutinib. As is typical for ibrutinib-based regimens, common grade =3 adverse events were most prevalent in the first 6 months of ibrutinib plus obinutuzumab treatment and generally decreased over time, except for hypertension. In this final analysis with up to 52 months of follow-up (median 45 months), ibrutinib plus obinutuzumab showed sustained clinical benefit, in terms of progression-free survival, in first-line treatment of chronic lymphocytic leukemia, including in patients with high-risk features. ClinicalTrials.gov identifier: NCT02264574. © 2022 Ferrata Storti Foundation.

Filiaciones:
Moreno C.:
 Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain

 Josep Carreras Leukemia Research Institute, Barcelona, Spain

Greil R.:
 3rd Medical Department, Paracelsus Medical University, Salzburg Cancer Research Institute-CCCIT, Salzburg, Austria

Demirkan F.:
 Dokuz Eylul University, Division of Hematology, Izmir, Turkey

Tedeschi A.:
 Niguarda Ca Granda Hospital, Milan, Italy

Anz B.:
 Tennessee Oncology, Chattanooga, TN, United States

Larratt L.:
 University of Alberta Hospital, Edmonton, AB, Canada

Simkovic M.:
 Department of Internal Medicine, Haematology, University Hospital and Medical School Hradec, Králové, Czech Republic

Novak J.:
 University Hospital Kralovske Vinohrady and Third Faculty of Medicine, Charles University, Prague, Czech Republic

Strugov V.:
 Almazov National Medical Research Centre, St. Petersburg, Russian Federation

Gill D.:
 Princess Alexandra Hospital, Brisbane, QLD, Australia

Gribben J.G.:
 Barts Cancer Institute, London, United Kingdom

Kwei K.:
 Pharmacyclics LLC, An AbbVie Company, Sunnyvale, CA, United States

Dai S.:
 Pharmacyclics LLC, An AbbVie Company, Sunnyvale, CA, United States

Hsu E.:
 Pharmacyclics LLC, An AbbVie Company, Sunnyvale, CA, United States

Dean J.P.:
 Pharmacyclics LLC, An AbbVie Company, Sunnyvale, CA, United States

Flinn I.W.:
 Sarah Cannon Research Institute, Nashville, TN, United States
ISSN: 07182295
Editorial
FERRATA STORTI FOUNDATION, VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY, Italia
Tipo de documento: Article
Volumen: 107 Número: 9
Páginas: 2108-2120
WOS Id: 000922919100013
ID de PubMed: 35021599
imagen All Open Access, Bronze

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