Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN

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.

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Journal
Blood
Published
2025-04-08
DOI
https://doi.org/10.1182/blood.2024024476
Citations
19
Primary Topic
Chronic Lymphocytic Leukemia Research
Type
article
Field-Weighted Citation Impact
30.88

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article

Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN

Manali Kamdar, John C. Byrd, Ian W. Flinn, Renata J. Walewska et al.
19 citations
Blood
Chronic Lymphocytic Leukemia Research
30.88
article

Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN

Manali Kamdar, John C. Byrd, Ian W. Flinn, Renata J. Walewska, Alan P Skarbnik, George Follows, Jeff Porter Sharman, Jennifer Ann Woyach, Yair Herishanu, Talha Munir, Alessandra Ferrajoli, Miklós Egyed, Krish Patel, Versha Banerji, Veerendra Munugalavadla, Marie Hughes, Laura Fogliatto, Catherine Wangui Wachira, Ann Janssens, Paulo Miranda, Paolo Ghia, Patricia Walker, Batul T. Suterwala, Emmanuelle Ferrant, Wojciech J. Jurczak, William G. Wierda, Chuan‐Chuan Wun
article en
19 citations

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.

BloodVol. 146(11)
The University of Texas MD Anderson Cancer Center (US), Vita-Salute San Raffaele University (IT), Tel Aviv Sourasky Medical Center (IL), St James's University Hospital (GB), Novant Health (US), Cambridge University Hospitals NHS Foundation Trust (GB), CancerCare Manitoba (CA), Swedish Medical Center (US), Hospital de Clínicas de Porto Alegre (BR), Tauranga Hospital (NZ), Somogy Megyei Kaposi Mór Oktató Kórház (HU), Sarah Cannon (US), San Francisco Public Library (US), Hôpital Lyon Sud (FR), National Institute of Oncology (HU), Peninsula Health (AU), AstraZeneca (Japan) (JP), IRCCS Ospedale San Raffaele (IT), University of Colorado Cancer Center (US), Tennessee Oncology (US), AstraZeneca (Poland) (PL), Willamette Valley Cancer Institute and Research Center (US), AstraZeneca (United States) (US), The Maria Sklodowska-Curie National Research Institute of Oncology (PL), Addenbrooke's Hospital (GB), Research Institute in Oncology and Hematology (CA), University of Manitoba (CA), The Ohio State University (US), University of Cincinnati (US), University of Colorado Denver (US), Bournemouth University (GB), KU Leuven (BE)
Pfizer, AstraZeneca, Gilead Sciences, National Comprehensive Cancer Network, National Institutes of Health, National Cancer Institute
Openalex Percentile: Top 0%
Chronic Lymphocytic Leukemia Research
30.88
DOIOpen Access PDFOpenAlex
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