First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia

作者：Barbara Eichhorst, Carsten Utoft Niemann, Arnon P. Kater, Moritz Fürstenau, Julia von Tresckow, Can Zhang, Sandra Robrecht, Michael Gregor, Gunnar Juliusson, Patrick Thornton, Philipp B. Staber, Tamar Tadmor, Vesa Lindström, Caspar da Cunha‐Bang, Christof Schneider, Christian Bjørn Poulsen, Thomas Illmer, Björn Schöttker, Thomas Nösslinger, Ann Janssens, Ilse Christiansen, Michaël Baumann, Henrik Frederiksen, Marjolein van der Klift, Ulrich Jäger, Maria B. L. Leys, Mels Hoogendoorn, Kourosh Lotfi, Holger Hebart, Tobias Gaska, Harry R. Koene, Lisbeth Enggaard, Jereon Goede, Josien C. Regelink, Anouk Widmer, Florian Simon, Nisha De Silva, Anna‐Maria Fink, Jasmin Bahlo, Kirsten Fischer, Clemens‐Martin Wendtner, Karl Anton Kreuzer, Matthias Ritgen, Monika Brüggemann, Eugen Tausch, Mark‐David Levin, Marinus van Oers, Christian H. Geisler, Stephan Stilgenbauer, Michael Hallek · 发表于：New England Journal of Medicine · 年份：2023 · DOI：10.1056/nejmoa2213093 · 被引用次数：308 · 研究领域：Chronic Lymphocytic Leukemia Research、Phagocytosis and Immune Regulation、HER2/EGFR in Cancer Research

Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking. Download a PDF of the Research Summary. In a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of chemoimmunotherapy (fludarabine–cyclophosphamide–rituximab or bendamustine–rituximab) or 12 cycles of venetoclax–rituximab, venetoclax–obinutuzumab, or venetoclax–obinutuzumab–ibrutinib. Ibrutinib was discontinued after two consecutive measurements of undetectable minimal residual disease or could be extended. The primary end points were undetectable minimal residual disease (sensitivity, <10−4 [i.e., <1 CLL cell in 10,000 leukocytes]) as assessed by flow cytometry in peripheral blood at month 15 and progression-free survival. A total of 926 patients were assigned to one of the four treatment regimens (229 to chemoimmunotherapy, 237 to venetoclax–rituximab, 229 to venetoclax–obinutuzumab, and 231 to venetoclax–obinutuzumab–ibrutinib). At month 15, the percentage of patients with undetectable minimal residual disease was significantly higher in the venetoclax–obinutuzumab group (86.5%; 97.5% confidence interval [CI], 80.6 to 91.1) and the venetoclax–obinutuzumab–ibrutinib group (92.2%; 97.5% CI, 87.3 to 95.7) than in the chemoimmunotherapy group (52.0%; 97.5% CI, 44....