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

作者：Jeff P. Sharman, Miklós Egyed, Wojciech Jurczak, Alan P Skarbnik, Krish Patel, Ian W. Flinn, Manali Kamdar, Talha Munir, Renata Walewska, Marie Hughes, Laura Fogliatto, Yair Herishanu, Versha Banerji, George Follows, Patricia Walker, Paolo Ghia, Ann Janssens, John C. Byrd, Emmanuelle Ferrant, Alessandra Ferrajoli, William G. Wierda, Catherine Wangui Wachira, Batul T. Suterwala, Paulo Miranda, Veerendra Munugalavadla, Chuan‐Chuan Wun, Jennifer A. Woyach · 发表于：Blood · 年份：2025 · DOI：10.1182/blood.2024024476 · 被引用次数：42 · 研究领域：Chronic Lymphocytic Leukemia Research

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) oc...