Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia

作者：Jennifer R. Brown, John F. Seymour, Wojciech Jurczak, Andrew Aw, Małgorzata Wach, Árpád Illés, Alessandra Tedeschi, Carolyn Owen, Alan P Skarbnik, Daniel Lysák, Ki-Seong Eom, Martin Šimkovič, Miguel Arturo Pavlovsky, Arnon P. Kater, Barbara Eichhorst, Kara Miller, Veerendra Munugalavadla, Ting Yu, Marianne de Borja, Paolo Ghia · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2409804 · 被引用次数：120 · 研究领域：Chronic Lymphocytic Leukemia Research、Phagocytosis and Immune Regulation、Chronic Myeloid Leukemia Treatments

BackgroundWhether fixed-duration acalabrutinib–venetoclax (with or without obinutuzumab) would result in better progression-free survival than chemoimmunotherapy in patients with untreated chronic lymphocytic leukemia (CLL) is unknown. MethodsIn this phase 3, open-label trial, we included patients 18 years of age or older who had an Eastern Cooperative Oncology Group performance-status score of 0 to 2 (range, 0 to 5, with higher numbers indicating greater disability) and who did not have a 17p deletion or TP53 mutation. Patients were randomly assigned, in a 1:1:1 ratio, to receive acalabrutinib–venetoclax (acalabrutinib, cycles 1 to 14; venetoclax, cycles 3 to 14), acalabrutinib–venetoclax–obinutuzumab (as above, plus obinutuzumab, cycles 2 to 7), or chemoimmunotherapy with the investigator’s choice of fludarabine–cyclophosphamide–rituximab or bendamustine–rituximab (cycles 1 to 6). The primary end point was progression-free survival (acalabrutinib–venetoclax vs. chemoimmunotherapy) in the intention-to-treat population, assessed by blinded independent central review. Research Summary Fixed-Duration Acalabrutinib Combinations in Untreated CLL ResultsA total of 867 patients underwent randomization: 291 were assigned to receive acalabrutinib–venetoclax, 286 acalabrutinib–venetoclax–obinutuzumab, and 290 chemoimmunotherapy (of whom 143 received fludarabine–cyclophosphamide–rituximab and 147 bendamustine–rituximab). The median age of the patients was 61 years (range, 26 to 86), 64...