Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL)

Authors

  • Oliver G. Ottmann MD,

    Corresponding author
    1. Departments of Hematology and Oncology, University Hospital of Frankfürt, Germany
    • Medizinische Klinik II, Abteilung Hamatologie und Onkologie, Johann Wolfgang Goethe University, Theodor Stern-Kai 7, 60590 Frankfurt, Germany
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    • O.G. Ottmann and B. Wassmann contributed equally.

    • O.G.O. and D.H. received research support from Novartis and served as consultants.

    • Fax: (011) 49-69-6301-7463.

  • Barbara Wassmann MD,

    1. Departments of Hematology and Oncology, University Hospital of Frankfürt, Germany
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    • O.G. Ottmann and B. Wassmann contributed equally.

  • Heike Pfeifer MD,

    1. Departments of Hematology and Oncology, University Hospital of Frankfürt, Germany
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    • H.P. performed research, A.G., M.S., U.D., M.S., L.W. enrolled and treated patients

  • Aristoteles Giagounidis MD,

    1. Departments of Hematology and Oncology, St. Johannes Hospital, Duisburg, Germany
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    • H.P. performed research, A.G., M.S., U.D., M.S., L.W. enrolled and treated patients

  • Matthias Stelljes MD,

    1. Departments of Hematology and Oncology, University Hospital of Münster, Germany
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    • H.P. performed research, A.G., M.S., U.D., M.S., L.W. enrolled and treated patients

  • Ulrich Dührsen MD,

    1. Departments of Hematology and Oncology, University Hospital of Essen, Germany
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    • H.P. performed research, A.G., M.S., U.D., M.S., L.W. enrolled and treated patients

  • Marc Schmalzing MD,

    1. Departments of Hematology and Oncology, University Hospital of Tübingen, Germany
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    • H.P. performed research, A.G., M.S., U.D., M.S., L.W. enrolled and treated patients

  • Lydia Wunderle MD,

    1. Departments of Hematology and Oncology, University Hospital of Frankfürt, Germany
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    • H.P. performed research, A.G., M.S., U.D., M.S., L.W. enrolled and treated patients

  • Anja Binckebanck,

    1. Departments of Hematology and Oncology, University Hospital of Frankfürt, Germany
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    • A.B. coordinated the study and managed and analyzed data

  • Dieter Hoelzer MD

    1. Departments of Hematology and Oncology, University Hospital of Frankfürt, Germany
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    • O.G.O. and D.H. received research support from Novartis and served as consultants.

    • D.H. designed the study and wrote the article


  • In addition to the authors, the following investigators participated in the trial: Phillip le Coutre, MD (Charite, Berlin), Joachim Beck, MD (University of Mainz), Mohammed Wattad, MD (Krankenhaus Essen-Werden), Matthias Schmid, MD (University of Ulm), Michael Lubbert, MD (University of Freiburg), Manfred Planker, MD, Matthias Freund, MD (University of Rostock), Stefan Schwartz, MD (Charite, Campus Benjamin Franklin, Berlin), Nicola Goekbuget, MD (University of Frankfurt), Harald Gschaidmeier, MD (Novartis Pharma, Nurnberg), Wolfram Brugger (Krankenhaus Villingen-Schwenningen), P. Duwel (Gutersloh), Winfried Gassmann (Siegen), A. Gruneisen (Berlin), E. Hagenreiner (Traunstein), Michael Kneba, MD (University of Kiel), A. Matylis, MD (Berlin), Andreas Neubauer (University of Marburg), Jolanta Perz (University of Heidelberg), M. Pfreundschuh (University Homburg/Saar); M. Planker (Stadtische Kliniken Krefeld), C. Schimmelpfennig (Oldenburg), and Andreas Thiel, MD (Chemnitz).

Abstract

BACKGROUND

Elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) have a poor prognosis, with a low complete remission (CR) rate, high induction mortality, and short remission duration. Imatinib (IM) has a favorable toxicity profile but limited antileukemic activity in advanced Ph+ALL. Imatinib in combination with intensive chemotherapy has yielded promising results as front-line therapy, but its value as monotherapy in newly diagnosed Ph+ALL is not known.

METHODS

Patients with de novo Ph+ALL were randomly assigned to induction therapy with either imatinib (IndIM) or multiagent, age-adapted chemotherapy (Indchemo). Imatinib was subsequently coadministered with consolidation chemotherapy.

RESULTS

In all, 55 patients (median age, 68 years) were enrolled. The overall CR rate was 96.3% in patients randomly assigned to IndIM and 50% in patients allocated to Indchemo (P = .0001). Nine patients (34.6%) were refractory and 2 patients died during Indchemo; none failed imatinib induction. Severe adverse events were significantly more frequent during Indchemo (90% vs 39%; P = .005). The estimated overall survival (OS) of all patients was 42% ± 8% at 24 months, with no significant difference between the 2 cohorts. Median disease-free survival was significantly longer in the 43% of patients (21 of 49 evaluable) in whom BCR-ABL transcripts became undetectable (18.3 months vs 7.2 months; P = .002).

CONCLUSIONS

In elderly patients with de novo Ph+ALL, imatinib induction results in a significantly higher CR rate and lower toxicity than induction chemotherapy. With subsequent combined imatinib and chemotherapy consolidation, this initial benefit does not translate into improved survival compared with chemotherapy induction. Cancer 2007. © 2007 American Cancer Society.

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