Phase II Study of Acalabrutinib, Venetoclax, and Obinutuzumab in a Treatment-Naïve Chronic Lymphocytic Leukemia Population Enriched for High-Risk Disease

作者：Matthew Steven Davids, Christine E. Ryan, Benjamin L. Lampson, Yue Ren, Svitlana Tyekucheva, Stacey M. Fernandes, Jennifer Leigh Crombie, Austin I. Kim, Matthew J. Weinstock, Josie S. Montegaard, Heather A. Walker, Claire Greenman, Victoria Patterson, Caron Alyce Jacobson, Ann Steward LaCasce, Philippe A. Armand, David Christopher Fisher, Steve Lo, Adam J. Olszewski, Jon E. Arnason, Inhye E. Ahn, Jennifer R. Brown · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco-24-02503 · 被引用次数：40 · 研究领域：Chronic Lymphocytic Leukemia Research、Chronic Myeloid Leukemia Treatments、Phagocytosis and Immune Regulation

PURPOSE The AMPLIFY trial recently established fixed-duration acalabrutinib, venetoclax, and obinutuzumab (AVO) as a new standard-of-care option for patients with previously untreated chronic lymphocytic leukemia (CLL) with wild-type TP53 ; however, due to the chemoimmunotherapy control arm, AMPLIFY excluded patients with high-risk TP53 aberration, for whom current standards of care are continuous Bruton tyrosine kinase inhibitor therapy or alternatively fixed-duration venetoclax-based doublets. AVO has not previously been evaluated in patients with CLL with TP53 aberration. METHODS This investigator-sponsored, multicenter, phase II study enrolled patients with treatment-naïve CLL enriched for high-risk CLL, defined by TP53 aberration (ClinicalTrials.gov identifier: NCT03580928 ). Patients received acalabrutinib, obinutuzumab, and then venetoclax, with each treatment introduced sequentially and in combination, with the duration guided by measurable residual disease (MRD). Patients who achieved undetectable MRD (uMRD) after either 15 or 24 cycles could discontinue treatment. The primary end point was complete remission (CR) with bone marrow uMRD (BM-uMRD) at the start of cycle 16. RESULTS Seventy-two patients were accrued, including 45 patients with TP53 aberration. The CR with BM-uMRD rates at the start of cycle 16 were 42% in patients with TP53 aberration and 42% in all-comers, and the BM-uMRD rates were 71% and 78%, respectively. Hematologic toxicities were mainly low grade...