Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN
Abstract
Abstract Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia. We present results from ELEVATE-TN after a median follow-up of 74.5 months. Overall, 535 patients were randomized (acalabrutinib-obinutuzumab, n = 179; acalabrutinib, n = 179; chlorambucil-obinutuzumab, n = 177). Median age was 70 years, 63.0% had unmutated immunoglobulin heavy chain variable region gene (uIGHV), 13.6% had del(17p) and/or mutated TP53, and 17% had complex karyotype (CK; ≥3 chromosomal abnormalities). Median progression-free survival (PFS) was not reached (NR) for acalabrutinib-obinutuzumab and acalabrutinib vs 27.8 months for chlorambucil-obinutuzumab (both P < .0001); estimated 72-month overall PFS rates were 78.0%, 61.5%, and 17.2%, respectively. Acalabrutinib-obinutuzumab resulted in improved PFS vs acalabrutinib monotherapy (hazard ratio [HR], 0.58; P = .0229). Patients with uIGHV, del(17p) and/or mutated TP53, or CK had significantly improved PFS with acalabrutinib ± obinutuzumab vs chlorambucil-obinutuzumab (P < .0001, P ≤ .0009, and P < .0001 for both acalabrutinib-containing arms, respectively). Median overall survival (OS) was NR for all treatments, with significantly longer OS for acalabrutinib-obinutuzumab than chlorambucil-obinutuzumab (HR, 0.62; P = .0349). Estimated 72-month OS rates were 83.9%, 75.5%, and 74.7% for acalabrutinib-obinutuzumab, acalabrutinib, and chlorambucil-obinutuzumab, respectively. Adverse events (AEs) occurring after >4 years were mostly grade 1 to 2. Rates of AEs, serious AEs, and events of clinical interest were similar between acalabrutinib-containing arms and consistent with the known safety profiles of acalabrutinib and obinutuzumab. Efficacy and safety of acalabrutinib-containing arms were maintained, with longer PFS in both acalabrutinib arms than chlorambucil-obinutuzumab including in patients with high-risk features. This trial was registered at www.ClinicalTrials.gov as #NCT02475681.
Article Details
Authors (27)
Jeff P. Sharman
1Willamette Valley Cancer Institute, Sarah Cannon Research, Eugene, OR
Miklos Egyed
Somogy County Moritz Kaposi General Hospital, Kaposvár, Hungary
Wojciech Jurczak
Alan Skarbnik
19Novant Health Cancer Institute, Department of Hematology, Charlotte, United States
Krish Patel
C. U. Shah Medical College, Surendranagar, India
Ian W. Flinn
6Tennessee Oncology, Nashville, TN
Manali Kamdar
Talha Munir
12St. James's University Hospital, Department of Haematology, Leeds, United Kingdom
Renata Walewska
20University Hospitals Dorset NHS Foundation Trust, Bournemouth, United Kingdom
Marie Hughes
10Tauranga Hospital, Tauranga, New Zealand
Laura Maria Fogliatto
11Department of Clinical Hematology, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil
Yair Herishanu
13Faculty of Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel
Versha Banerji
8Paul Albrechtsen Research Institute and Department of Medical Oncology & Hematology, CancerCare Manitoba, and Department of Internal Medicine, Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
George Follows
14Department of Haematology, Addenbrooke’s Hospital NHS Trust, Cambridge, United Kingdom
Patricia Walker
9Peninsula Health and Peninsula Private Hospital, Melbourne, Australia
Paolo Ghia
School of Medicine, Università Vita Salute San Raffaele, Milan
Ann Janssens
Universitaire Ziekenhuizen Leuven, Leuven, Belgium
John C. Byrd
Emmanuelle Ferrant
3Department of Hematology, Hôpital Lyon-Sud, Lyon, France
Alessandra Ferrajoli
1University of Texas MD Anderson Cancer Center, Leukemia, Houston, United States
William G. Wierda
The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Catherine Wangui Wachira
23AstraZeneca, South San Francisco, CA
Batul T. Suterwala
24AstraZeneca, Gaithersburg, MD
Paulo Miranda
24AstraZeneca, Gaithersburg, MD
Veerendra Munugalavadla
14AstraZeneca, South San Francisco, United States
Chuan-Chuan Wun
24AstraZeneca, Gaithersburg, MD
Jennifer A. Woyach
5Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH