• Barbara Eichhorst, Carsten U 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 B Poulsen, Thomas Illmer, Björn Schöttker, Thomas Nösslinger, Ann Janssens, Ilse Christiansen, Michael Baumann, Henrik Frederiksen, Marjolein van der Klift, Ulrich Jäger, Maria B L Leys, Mels Hoogendoorn, Kourosh Lotfi, Holger Hebart, Tobias Gaska, Harry 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 A Kreuzer, Matthias Ritgen, Monika Brüggemann, Eugen Tausch, Mark-David Levin, Marinus van Oers, Christian Geisler, Stephan Stilgenbauer, Michael Hallek, and GCLLSG, the HOVON and Nordic CLL Study Groups, the SAKK, the Israeli CLL Association, and Cancer Trials Ireland.
• From the Department I of Internal Medicine, Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne (B.E., M.F., C.Z., S.R., F.S., A.-M.F., J.B., K.F., K.A.K., M. Hallek), the Clinic for Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen (J.T.), the Division of Chronic Lymphocytic Leukemia, Department of Internal Medicine III, University of Ulm, Ulm (C.S., E.T., S.S.), Group Practice for Hematology and Oncology, Dresden (T.I.); the Hematology-Oncology Center, Würzburg (B.S.), Specialist Medical Practice of Hematology and Oncology, Mutlangen (H.H.), the Department of Hematology, Clinic for Hematology and Oncology, Centrum of Oncology, Brüderhospital St. Josef, Paderborn (T.G.), the Munich Clinic Schwabing, Academic Teaching Hospital, Ludwig Maximilian University, Munich (C.-M.W.); and the Department of Hematology, University Hospital Schleswig-Holstein, Campus Kiel (M.R., M. Brüggemann), Kiel - all in Germany; the Department of Hematology, Odense Rigshospitalet, Copenhagen University Hospital (C.U.N., C.C.-B., C.G.), and the Department of Hematology, Center for Cancer and Organ Diseases, Rigshospitalet (L.E.),Copenhagen, the Department of Hematology, Faculty of Medicine, Aalborg University Hospital, Aalborg (I.C.), the Department of Hematology, Zealand University Hospital, Roskilde (C.B.P.), and the Department of Hematology, Odense University Hospital, Odense (H.F.) - all in Denmark; the Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Center, University of Amsterdam, Amsterdam (A.P.K., M.O.), the Department of Internal Medicine, Amphia Hospital, Breda (M.K.), the Department of Hematology, Maasstad Ziekenhuis, Rotterdam (M.B.L.L.), the Department of Hematology and Oncology, Medical Center Leeuwarden, Leeuwarden (M. Hoogendoorn), the Department of Hematology, St. Antonius Hospital Utrecht, Utrecht (H.K.), the Department of Hematology, Meander Medical Center, Amersfoort (J.C.R.), and the Department of Hematology, Albert Schweitzer Hospital, Dordrecht (M.-D.L.) - all in the Netherlands; the Department of Hematology, Luzerner Kantonsspital, Lucerne (M.G.), the Department of Hematology, Kantonsspital St. Gallen, St. Gallen (M. Baumann), the Department of Hematology, Clinic for Medical Oncology and Hematology, Kantonsspital Hospital Winterthur, Winterthur (J.G.), and the Department of Medical Oncology and Hematology Clinic, University Hospital Zürich, Zürich (A.W.) - all in Switzerland; the Department of Hematology, Lund University Cancer Center, Lund (G.J.), and the Department of Hematology, Linköping University Hospital, Linköping (K.L.) - both in Sweden; the Department of Hematology, Blackrock Health Member Hospitals, Hermitage Clinic, Dublin (P.T.); the Department of Medicine I, Division of Hematology and Hemostaseology (P.B.S.), the Department of Internal Medicine, University Hospital for Internal Medicine, Clinical Department of Hematology and Hemostaseology (U.J.), and the Comprehensive Cancer Center Vienna, Vienna General Hospital (P.B.S.), Medical University of Vienna, and the Department of Hematology and Oncology, Hanusch Hospital (T.N.) - both in Vienna; the Department of Hematology and Blood Bank, Bnai Zion Medical Center, Haifa, Israel (T.T.); the Department of Hematology, Comprehensive Cancer Center, Helsinki University Hospital, Helsinki (V.L.); the Department of Oncology, Universitair Ziekenhuis Leuven, Leuven, Belgium (A.J.); and the Department of Hematology, University College London, London (N.D.S.).
• N. Engl. J. Med. 2023 May 11; 388 (19): 173917541739-1754.

BackgroundRandomized 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.MethodsIn 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.ResultsA 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, 44.4 to 59.5; P<0.001 for both comparisons), but it was not significantly higher in the venetoclax-rituximab group (57.0%; 97.5% CI, 49.5 to 64.2; P = 0.32). Three-year progression-free survival was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the chemoimmunotherapy group (hazard ratio for disease progression or death, 0.32; 97.5% CI, 0.19 to 0.54; P<0.001). Progression-free survival at 3 years was also higher with venetoclax-obinutuzumab (87.7%; hazard ratio for disease progression or death, 0.42; 97.5% CI, 0.26 to 0.68; P<0.001), but not with venetoclax-rituximab (80.8%; hazard ratio, 0.79; 97.5% CI, 0.53 to 1.18; P = 0.18). Grade 3 and grade 4 infections were more common with chemoimmunotherapy (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) than with venetoclax-rituximab (10.5%) or venetoclax-obinutuzumab (13.2%).ConclusionsVenetoclax-obinutuzumab with or without ibrutinib was superior to chemoimmunotherapy as first-line treatment in fit patients with CLL. (Funded by AbbVie and others; GAIA-CLL13 ClinicalTrials.gov number, NCT02950051; EudraCT number, 2015-004936-36.).Copyright © 2023 Massachusetts Medical Society.

33 keywords...

hide…