Zanubrutinib Versus Bendamustine and Rituximab in Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Median 5-Year Follow-Up of SEQUOIA
Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. SEQUOIA (ClinicalTrials.gov identifier: NCT03336333 ) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.2 months) and subsequent analysis (43.7 months) found superior progression-free survival (PFS; the primary end point) in patients who received zanubrutinib compared with BR. At a median follow-up of 61.2 months, median PFS was not reached in zanubrutinib-treated patients; median PFS was 44.1 months in BR-treated patients (hazard ratio [HR], 0.29; one-sided P = .0001). Prolonged PFS was seen with zanubrutinib versus BR in patients with mutated immunoglobulin heavy-chain variable region (IGHV) genes (HR, 0.40; one-sided P = .0003) and unmutated IGHV genes (HR, 0.21 [95% CI, 0.14 to 0.33]; one-sided P < .0001). Median overall survival (OS) was not reached in either treatment arm; estimated 60-month OS rates were 85.8% and 85.0% in zanubrutinib- and BR-treated patients, respectively. No new safety signals were detected. Adverse events were as expected with zanubrutinib; rate of atrial fibrillation was 7.1%. At a median follow-up of 61.2 months, the results supported the initial SEQUOIA findings and suggested that zanubrutinib was a favorable treatment option for untreated patients with CLL/SLL.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (33)
Mazyar Shadman
Talha Munir
12St. James's University Hospital, Department of Haematology, Leeds, United Kingdom
Tadeusz Robak
36Department of Hematology, Medical University of Lodz, Lodz, Poland
Jennifer R. Brown
Brad S. Kahl
30Division of Oncology, Washington University School of Medicine, St. Louis, MO
Paolo Ghia
School of Medicine, Università Vita Salute San Raffaele, Milan
Krzysztof Giannopoulos
14Medical University of Lublin, Department of Experimental Hematooncology, Lublin, Poland
Martin Simkovic
254th Department of Internal Medicine-Hematology, Faculty of Medicine in Hradec Kralove, University Hospital and Charles University, Hradec Kralove, Hradec Kralove, Czech Republic
Anders Österborg
28Karolinska Institute and Karolinska University Hospital, Stockholm, United States
Luca Laurenti
2Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology, Agostino Gemelli University Hospital Foundation IRCCS, Rome, Italy
Patricia A. Walker
Peninsula Health and Peninsula Private Hospital, Frankston, Melbourne, VIC, Australia
Stephen S. Opat
Lymphoma Research Group, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia
Hanna Ciepluch
Department of Hematology, Copernicus Regional Oncology Centre, Gdansk, Poland
Richard Greil
Merit Hanna
9North Shore Hospital, Waitemata District Health Board, Auckland, New Zealand
Monica Tani
14Hematology Unit, Department of Oncology and Hematology, “Santa Maria delle Croci” Hospital, Ravenna, Italy
Marek Trneny
Danielle Brander
2Duke University, Div of Hematologic Malignancies & Cellular Therapy, Durham, United States
Ian W. Flinn
6Tennessee Oncology, Nashville, TN
Sebastian Grosicki
Department of Cancer Prevention, Medical University of Silesia, Katowice, Poland
Emma Verner
5Concord Repatriation General Hospital, Concord, Australia
Alessandra Tedeschi
2Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
Sophie de Guibert
27CHU Rennes, Rennes, France
Gayane Tumyan
2National Medical Research Center of Oncology named after N.N. Blokhin, Moscow, Russian Federation
Kamel Laribi
13CH du mans, Le Mans, France
José A. García-Marco
Unidad de Citogenetica Molecular, Servicio de Hematología, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain
Jian-Yong Li
The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
Tian Tian
Yu Liu
Roman Korolkiewicz
BeiGene USA, Inc, San Mateo, CA
Andy Szeto
BeiGene USA, Inc, San Mateo, CA
Constantine S. Tam
40Department of Haematology, Alfred Hospital and Monash University, Melbourne, VIC, Australia
Wojciech Jurczak