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First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia
Barbara Eichhorst1, Carsten U Niemann1, Arnon P Kater1
1From 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.).
First-line venetoclax-obinutuzumab, with or without ibrutinib, demonstrated superior outcomes compared to chemoimmunotherapy in fit patients with chronic lymphocytic leukemia (CLL). This study highlights advanced treatment options for CLL patients.
Area of Science:
- Oncology
- Hematology
- Clinical Trials
Background:
- Lack of randomized trials evaluating venetoclax plus anti-CD20 antibodies as first-line therapy for fit patients with advanced chronic lymphocytic leukemia (CLL).
- Need for comparative data on novel targeted therapies versus traditional chemoimmunotherapy in this patient population.
Purpose of the Study:
- To compare the efficacy and safety of venetoclax-based regimens against chemoimmunotherapy in previously untreated, fit patients with advanced CLL.
- To assess rates of undetectable minimal residual disease and progression-free survival.
Main Methods:
- Phase 3, open-label, randomized trial involving 926 fit CLL patients without TP53 aberrations.
- Patients were assigned to chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) or venetoclax combined with rituximab, obinutuzumab, or obinutuzumab-ibrutinib.
- Primary endpoints included undetectable minimal residual disease by flow cytometry at 15 months and progression-free survival.
Main Results:
- Venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib achieved significantly higher rates of undetectable minimal residual disease at 15 months compared to chemoimmunotherapy (86.5% and 92.2% vs. 52.0%).
- Three-year progression-free survival was superior with venetoclax-obinutuzumab-ibrutinib (90.5%) and venetoclax-obinutuzumab (87.7%) versus chemoimmunotherapy (75.5%).
- Higher rates of grade 3/4 infections were observed with chemoimmunotherapy (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) compared to venetoclax-rituximab (10.5%) and venetoclax-obinutuzumab (13.2%).
Conclusions:
- First-line treatment with venetoclax-obinutuzumab, with or without ibrutinib, is superior to chemoimmunotherapy in fit patients with advanced CLL.
- These findings support the use of venetoclax-based combinations as a preferred first-line strategy for eligible CLL patients.
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