O.G. Ottmann and B. Wassmann contributed equally.
Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL)†
Article first published online: 11 APR 2007
Copyright © 2007 American Cancer Society
Volume 109, Issue 10, pages 2068–2076, 15 May 2007
How to Cite
Ottmann, O. G., Wassmann, B., Pfeifer, H., Giagounidis, A., Stelljes, M., Dührsen, U., Schmalzing, M., Wunderle, L., Binckebanck, A. and Hoelzer, D. (2007), Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Cancer, 109: 2068–2076. doi: 10.1002/cncr.22631
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).
- Issue published online: 25 APR 2007
- Article first published online: 11 APR 2007
- Manuscript Accepted: 11 JAN 2007
- Manuscript Revised: 7 JAN 2007
- Manuscript Received: 18 DEC 2006
- BMBF Competence Network “Acute Leukemias”. Grant Number: 01G19971
- German Genome Research Network (NGFN)
- Wilhelm Sander Stiftung and the Adolf-Messer Foundation, Germany
- Novartis Pharma AG, Nurnberg, Germany
- acute lymphoblastic leukemia;
- Philadelphia chromosome;
- minimal residual disease;
- randomized trial
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.
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.
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).
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.