Evidence map›Paper›PMID 29562156›Full record

Trial reportThe New England journal of medicine2018

Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia.

John F Seymour, Thomas J Kipps, Barbara Eichhorst, Peter Hillmen, James D'Rozario, Sarit Assouline, Carolyn Owen, John Gerecitano, Tadeusz Robak, Javier De la Serna and 10 more

2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 484 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
484citing papers in PubMed, 12 pooled it
67.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02005471 phase3completednot on this map

A Multicenter, Phase III, Open-Label, Randomized Study in Relapsed/Refractory Patients With Chronic Lymphocytic Leukemia to Evaluate the Benefit of Venetoclax (GDC-0199/ABT-199) Plus Rituximab Compared With Bendamustine Plus Rituximab

TypeinterventionalSponsorHoffmann-La RocheRan2014 to 2022Enrolled389ConditionsChronic Lymphocytic LeukemiaArmsBendamustine, Venetoclax, Rituximab
NCT03755947 phase2completednot on this map

Sequential Triple Therapy With Ibrutinib, Obinutuzumab and Venetoclax in First and Second Line for Patients With Chronic Lymphocytic Leukemia

TypeinterventionalSponsorGrupo Cooperativo de Hemopatías MalignasRan2018 to 2021Enrolled3ConditionsB-Cell Chronic Lymphocytic Leukemia, B-Cell Chronic Lymphocytic Leukemia in Relapse (Diagnosis)ArmsIbrutinib, Obinutuzumab, Venetoclax
3 · Its place in the literature

Who cites it

484 citing papers in PubMed, 12 syntheses or guidelines pooled it, 888 citations in OpenAlex.

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424 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 16 institutions in 11 countries.

John F SeymourFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Thomas J KippsFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Barbara EichhorstFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Peter HillmenFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
James D'RozarioFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Sarit AssoulineFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Carolyn OwenFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
John GerecitanoFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Tadeusz RobakFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Javier De la SernaFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Ulrich JaegerFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Guillaume CartronFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Marco MontilloFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Rod HumerickhouseFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Elizabeth A PunnooseFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Yan LiFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Michelle BoyerFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Kathryn HumphreyFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Mehrdad MobasherFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Arnon P KaterFrom the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Roche (United Kingdom) · GBAbbVie (United States) · USAcademic Medical Center · NLAustralian National University · AUAzienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda · ITCentre Hospitalier Universitaire de Montpellier · FRCopernicus Memorial Hospital · PLHospital Universitario 12 De Octubre · ESJewish General Hospital · CAMedical University of Vienna · ATMemorial Sloan Kettering Cancer Center · USSt James's University Hospital · GBUniversity Hospital Cologne · DEUniversity of Calgary · CAUniversity of California, San Diego · USUniversity of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundVenetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We evaluated the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia.

methodsIn this randomized, open-label, phase 3 trial, we randomly assigned 389 patients to receive venetoclax for up to 2 years (from day 1 of cycle 1) plus rituximab for the first 6 months (venetoclax-rituximab group) or bendamustine plus rituximab for 6 months (bendamustine-rituximab group). The trial design did not include crossover to venetoclax plus rituximab for patients in the bendamustine-rituximab group in whom progression occurred. The primary end point was investigator-assessed progression-free survival.

resultsAfter a median follow-up period of 23.8 months, the rate of investigator-assessed progression-free survival was significantly higher in the venetoclax-rituximab group (32 events of progression or death in 194 patients) than in the bendamustine-rituximab group (114 events in 195 patients); the 2-year rates of progression-free survival were 84.9% and 36.3%, respectively (hazard ratio for progression or death, 0.17; 95% confidence interval [CI], 0.11 to 0.25; P<0.001 by the stratified log-rank test). The benefit was maintained across all clinical and biologic subgroups, including the subgroup of patients with chromosome 17p deletion; the 2-year rate of progression-free survival among patients with chromosome 17p deletion was 81.5% in the venetoclax-rituximab group versus 27.8% in the bendamustine-rituximab group (hazard ratio, 0.13; 95% CI, 0.05 to 0.29), and the 2-year rate among those without chromosome 17p deletion was 85.9% versus 41.0% (hazard ratio, 0.19; 95% CI, 0.12 to 0.32). The benefit of venetoclax plus rituximab over bendamustine plus rituximab was confirmed by an independent review committee assessment of progression-free survival and other secondary efficacy end points. The rate of grade 3 or 4 neutropenia was higher in the venetoclax-rituximab group than in the bendamustine-rituximab group, but the rates of grade 3 or 4 febrile neutropenia and infections or infestations were lower with venetoclax than with bendamustine. The rate of grade 3 or 4 tumor lysis syndrome in the venetoclax-rituximab group was 3.1% (6 of 194 patients).

conclusionsAmong patients with relapsed or refractory chronic lymphocytic leukemia, venetoclax plus rituximab resulted in significantly higher rates of progression-free survival than bendamustine plus rituximab. (Funded by Genentech and AbbVie; ClinicalTrials.gov number, NCT02005471 .).

Indexed as

AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBendamustine HydrochlorideBridged Bicyclo Compounds, HeterocyclicDisease-Free SurvivalDrug Resistance, NeoplasmFemaleHumansKaplan-Meier EstimateLeukemia, Lymphocytic, Chronic, B-CellMaleMiddle AgedNeoplasm, ResidualNeutropeniaBendamustine HydrochlorideBridged Bicyclo Compounds, HeterocyclicRituximabSulfonamidesvenetoclax

Identifiers

PMID29562156
OpenAlexW2792666902

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