Final Evaluation of Randomized CML-Study IV: 10-Year Survival and Evolution of Terminal Phase-Reference-Cited by-同舟云学术

Final Evaluation of Randomized CML-Study IV: 10-Year Survival and Evolution of Terminal Phase

Published:2017-12-07 Issue:Suppl_1 Volume:130 Page:897-897
ISSN:0006-4971
Container-title:Blood
language:en
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Author:

Hehlmann Rüdiger¹,Lauseker Michael²,Saussele Susanne³,Pfirrmann Markus⁴,Krause Stefan W.⁵,Kolb Hans-Jochem⁶,Neubauer Andreas⁷,Hossfeld Dieter K.⁸,Nerl Christoph⁹,Gratwohl Alois¹⁰,Baerlocher Gabriela M.¹¹,Heim Dominik¹²,Bruemmendorf Tim Henrik¹³,Fabarius Alice¹,Haferlach Claudia¹⁴,Schlegelberger Brigitte¹⁵,Müller Martin C.¹,Jeromin Sabine¹⁶,Proetel Ulrike¹⁷,Kohlbrenner Katharina¹⁸,Voskanyan Astghik¹⁹,Rinaldetti Sébastien¹,Seifarth Wolfgang²⁰,Spiess Birgit²¹,Balleisen Leopold²²,Goebeler Maria E²³,Hänel Mathias²⁴,Ho Anthony D.²⁵,Dengler J²⁶,Falge C²⁷,Kanz Lothar²⁸,Köhne Claus-Henning²⁹,Burchert Andreas³⁰,Kneba Michael³¹,Stegelmann Frank³²,Köhne C³³,Lindemann Hans-Walter³⁴,Waller C³⁵,Pfreundschuh Michael³⁶³⁷,Spiekermann Karsten³⁸,Berdel Wolfgang E³⁹,Müller L⁴⁰,Edinger Matthias⁴¹,Mayer Jiri⁴²,Beelen Dietrich W⁴³,Bentz Martin⁴⁴,Link Hartmut⁴⁵,Hertenstein Bernd⁴⁶,Fuchs R⁴⁷,Wernli Martin⁴⁸,Schlegel F⁴⁹,Schlag Rudolph⁵⁰,de Wit M⁵¹,Trümper Lorenz⁵²,Hebarth H⁵³,Hahn M⁵⁴,Thomalla Jörg⁵⁵,Scheid Christof⁵⁶,Schafhausen Philippe⁵⁷,Verbeek Walter⁵⁸,Eckart Michael J.⁵⁹,Gassmann Winfried⁶⁰,Pezzutto Antonio⁶¹,Schenk Michael⁶²,Brossart Peter⁶³,Geer Thomas⁶⁴,Bildat Stephan⁶⁵,Schäfer E⁶⁶,Hochhaus Andreas⁶⁷,Hasford Joerg⁴

Affiliation:

1. III. Medizinische Klinik, Medizinische Fakultät Mannheim der Uni Heidelberg, Mannheim, Germany

2. Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität München, München, Germany

3. III. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany

4. Institut für medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität, München, Germany

5. Department of Internal Medicine 5, Haematology/Oncology, University of Erlangen, Erlangen, Germany

6. Department of Internal Medicine III, University of Munich-Grosshadern, Munich, Germany

7. Department of Hematology and Oncology, University Hospital Giessen and Marburg, Marburg, Germany

8. II. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg, Germany

9. Klinik für Hämatologie, Onkologie, Immunologie, Palliativmedizin, Infektiologie und Tropenmedizin, Klinikum Schwabing, München, Germany

10. Hematology, University Hospital of Basel, Basel, Switzerland

11. Universitätsklinik für Hämatologie und hämatologisches Zentrallabor, Inselspital, Bern, Switzerland

12. Klinik für Hämatologie, Universitätsspital, Basel, Switzerland

13. Direktor der Klinik für Onkologie, Hämatologie und Stammzelltransplantation Euregionales Comprehensive Cancer Center Aachen (ECCA), Aachen, Germany

14. MLL Munich Leukemia Laboratory GmbH, Munich, Germany

15. Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany

16. MLL Munich Leukemia Laboratory, Munich, Germany

17. III. Medizinische Klinik, Universität Heidelberg, Medizinische Fakultät, Mannheim, Germany

18. III. Med. Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany

19. Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany

20. Department of Hematology and Oncology, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany

21. University Hospital Mannheim, Heidelberg University, Department of Hematology and Oncology, Mannheim, Germany

22. Evangelisches Krankenhaus, Hamm, DEU

23. Leitung CCC Trial Office, Würzburg, Germany

24. Klinikum Chemnitz, Chemnitz, Germany

25. Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany

26. Schwerpunktpraxis Heildbronn, Heilbronn, Germany

27. Klinikum Nürnberg Nord, Nürnberg, Germany

28. Department of Oncology, Hematology, Immunology, Rheumatology and Pulmonology, University Hospital Tuebingen, Tuebingen, Germany, Tuebingen, Germany

29. Klinik für Onkologie und Hämatologie, Klinikum Oldenburg, Oldenburg, Germany

30. Hem./Onc./Immunology, University of Marburg, Marburg, Germany

31. Department of Internal Medicine II, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany

32. Department of Internal Medicine III, University Hospital of Ulm, Germany, Ulm, Germany

33. Klinik für Innere Medizin I, Universität des Saarlandes, Homburg, Homburg, Germany

34. Klinik für Hämatologie / Onkologie, Kath. Krankenhaus Hagen gem. GmbH - St.-Marien-Hospital, Hagen, Germany

35. Universitätsklinikum Freiburg, Freiburg, Germany

36. José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Universität des Saarlandes, Homburg, Germany

37. Innere Medizin I, Universität des Saarlandes, Homburg, Germany

38. Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany

39. Department of Medicine A - Hematology and Oncology, University Hospital of Muenster, Muenster, Germany

40. MLL München, München, Germany

41. Abteilung Hämatologie und Internistische Onkologie, Universitätsklinikum, Regensburg, Germany

42. Department of Internal Medicine, Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic

43. Department of Bone Marrow Transplantation, West German Cancer Center, University of Duisburg-Essen, Essen, Germany

44. Department of Internal Medicine III, Municipal Hospital of Karlsruhe, Karlsruhe, Germany

45. Medizinische Klinik I Westpfalz-Klinikum, Kaiserslautern, Germany

46. I. Medizinische Klinik, Klinikum Bremen-Mitte, Bremen, Germany

47. Medizinische Klinik IV, Uniklinik RWTH Aachen, Aachen, Germany

48. Onkologie/Hämatologie, Kantonsspital, Aarau, Switzerland

49. Schwerpunkt Hämatologie / Internistische Onkologie, Stauferklinikum Schwäbisch Gmünd, Mutlangen, Mutlangen, Germany

50. Ambulantes Onkologie-Zentrum, Ansbach, Wurzburg, DEU

51. Klinik I für Innere Medizin, Universitätsklinikum Köln, Köln, Germany

52. Department of Hematology and Oncology, Universitätsmedizin Göttingen, Georg-August-Universität, Göttingen, Germany

53. Internistische Schwerpunktpraxis Erlangen, Erlangen, Germany

54. Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie, Campus Benjamin Franklin, Charité, Berlin, Berlin, Germany

55. Praxisklinik für Hämatologie und Onkologie, Koblenz, Germany

56. University of Cologne, Cologne, Germany

57. Department of Hematology and Oncology with Sections BMT and Pneumology, Hubertus Wald Tumorzentrum, University Hospital Hamburg-Eppendorf, Hamburg, Germany

58. Center of Outpatient Hematology/Oncology, Bonn, Germany

59. Onkologische Schwerpunktpraxis Erlangen, Erlangen, Germany

60. St. Marien-Krankenhaus gGmbH, Siegen, Germany

61. Charite Research Organization, Berlin, Germany

62. Krankenhaus Barmherzige Brüder, Regensburg, Germany

63. Department of Internal Medicine III, Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany

64. Innere Medizin Hämatologie und Onkologie, Schwabisch Hall, Germany

65. Klinikum Herford, Herford, Germany

66. Onkologische Schwerpunktpraxis Bielefeld, Bielefeld, Germany

67. Jena University Hospital, Jena, Germany

Abstract

Abstract Background Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400mg/day (n=400) could be optimized by doubling the dose (n=420), adding IFN (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). Methods From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. The impact of patients' and disease factors on survival was prospectively analyzed. At the time of evaluation, at least 62% of patients still received imatinib, 26.2% were switched to 2nd generation tyrosine kinase inhibitors. Results After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival 80% and 10-year relative survival 92%. In spite of a faster response with IM800mg, the survival difference between IM400mg and IM800mg was only 3% at 5 years. In a multivariate analysis, the influence on survival of risk-group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs. other) was significant in contrast to any form of initial treatment optimization. Patients that reached the response milestones 3, 6 and 12 months, had a significant survival advantage of about 6% after 10 years regardless of therapy. The progression probability to blast crisis was 5.8%. Blast crisis was proceeded by high-risk additional chromosomal aberrations. Conclusions For responders, monotherapy with IM400mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease and blast crisis, more life-time can currently be gained by carefully addressing non-CML determinants of survival. Disclosures Hehlmann: Novartis: Research Funding; BMS: Consultancy. Saussele: Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Pfirrmann: BMS: Honoraria; Novartis: Honoraria. Krause: Novartis: Honoraria. Baerlocher: Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria. Bruemmendorf: Novartis: Research Funding. Müller: Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Ariad: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Jeromin: MLL Munich Leukemia Laboratory: Employment. Hänel: Roche: Honoraria; Novartis: Honoraria. Burchert: BMS: Honoraria. Waller: Mylan: Consultancy, Honoraria. Mayer: Eisai: Research Funding; Novartis: Research Funding. Link: Novartis: Honoraria. Scheid: Novartis: Honoraria. Schafhausen: Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Ariad: Honoraria. Hochhaus: Incyte: Research Funding; MSD: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; BMS: Research Funding; ARIAD: Research Funding.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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