First-line venetoclax combinations versus chemoimmunotherapy in fit patients with chronic lymphocytic leukaemia (GAIA/CLL13): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial

作者：Moritz Fürstenau, Arnon P. Kater, Sandra Robrecht, Julia von Tresckow, Can Zhang, Michael Gregor, Patrick Thornton, Philipp B. Staber, Tamar Tadmor, Vesa Lindström, Gunnar Juliusson, Ann Janssens, Mark‐David Levin, Caspar da Cunha‐Bang, Christof Schneider, Neta Goldschmidt, Elisabeth Vandenberghe, Davide Rossi, Rudolf Benz, Thomas Nösslinger, Daniel Heintel, Christian Bjørn Poulsen, Ilse Christiansen, Henrik Frederiksen, Lisbeth Enggaard, Eduardus F. M. Posthuma, Djamila E. Issa, Hein P. J. Visser, Mar Bellido, Nadine Kutsch, Jan Dürig, Alexander Stehle, Matthias Vöhringer, Sebastian Böttcher, Clemens Schulte, Florian Simon, Anna‐Maria Fink, Kirsten Fischer, Emily Eva Holmes, Karl‐Anton Kreuzer, Matthias Ritgen, Monika Brüggemann, Eugen Tausch, Stephan Stilgenbauer, Michael Hallek, Carsten Utoft Niemann, Barbara Eichhorst · 发表于：The Lancet Oncology · 年份：2024 · DOI：10.1016/s1470-2045(24)00196-7 · 被引用次数：84 · 研究领域：Chronic Lymphocytic Leukemia Research、Phagocytosis and Immune Regulation、Lymphoma Diagnosis and Treatment

Background In the primary analysis report of the GAIA/CLL13 trial, we found that venetoclax–obinutuzumab and venetoclax–obinutuzumab–ibrutinib improved undetectable measurable residual disease (MRD) rates and progression-free survival compared with chemoimmunotherapy in patients with previously untreated chronic lymphocytic leukaemia. However, to our knowledge, no data on direct comparisons of different venetoclax-based combinations are available. Methods GAIA/CLL13 is an open-label, randomised, phase 3 study conducted at 159 sites in ten countries in Europe and the Middle East. Eligible patients were aged 18 years or older, with a life expectancy of at least 6 months, an Eastern Cooperative Oncology group performance status of 0–2, a cumulative illness rating scale score of 6 or lower or a single score of 4 or lower, and no TP53 aberrations. Patients were randomly assigned (1:1:1:1), with a computer-generated list stratified by age, Binet stage, and regional study group, to either chemoimmunotherapy, venetoclax–rituximab, venetoclax–obinutuzumab, or venetoclax–obinutuzumab–ibrutinib. All treatments were administered in 28-day cycles. Patients in the chemoimmunotherapy group received six cycles of treatment, with patients older than 65 years receiving intravenous bendamustine (90 mg/m 2 , days 1–2), whereas patients aged 65 years or younger received intravenous fludarabine (25 mg/m 2 , days 1–3) and intravenous cyclophosphamide (250 mg/m 2 , days 1–3). Intravenous rituximab (...