Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants

被引：251

作者：

Hehlmann, R. ^{[1
]}

Lauseker, M. ^{[2
]}

Saussele, S. ^{[1
]}

Pfirrmann, M. ^{[2
]}

Krause, S. ^{[3
]}

Kolb, H. J. ^{[4
]}

Neubauer, A. ^{[5
]}

Hossfeld, D. K. ^{[6
]}

Nerl, C. ^{[7
]}

Gratwohl, A. ^{[8
]}

Baerlocher, G. M. ^{[9
]}

Heim, D. ^{[8
]}

Bruemmendorf, T. H. ^{[10
]}

Fabarius, A. ^{[1
]}

Haferlach, C. ^{[11
]}

Schlegelberger, B. ^{[12
]}

Mueller, M. C. ^{[1
]}

Jeromin, S. ^{[11
]}

Proetel, U. ^{[1
]}

Kohlbrenner, K. ^{[1
]}

Voskanyan, A. ^{[1
]}

Rinaldetti, S. ^{[1
]}

Seifarth, W. ^{[1
]}

Spiess, B. ^{[1
]}

Balleisen, L. ^{[13
]}

Goebeler, M. C. ^{[14
]}

Haenel, M. ^{[15
]}

Ho, A. ^{[16
]}

Dengler, J. ^{[17
]}

Falge, C. ^{[18
]}

Kanz, L. ^{[19
]}

Kremers, S. ^{[20
]}

Burchert, A. ^{[5
]}

Kneba, M. ^{[21
]}

Stegelmann, F. ^{[22
]}

Koehne, C. A. ^{[23
]}

Lindemann, H. W. ^{[24
]}

Waller, C. F. ^{[25
]}

Pfreundschuh, M. ^{[26
]}

Spiekermann, K. ^{[4
]}

Berdel, W. E. ^{[27
]}

Mueller, L. ^{[28
]}

Edinger, M. ^{[29
]}

Mayer, J. ^{[30
]}

Beelen, D. W. ^{[31
]}

Bentz, M. ^{[32
]}

Link, H. ^{[33
]}

Hertenstein, B. ^{[34
]}

Fuchs, R. ^{[10
]}

Wernli, M. ^{[35
]}

机构：

[1] Heidelberg Univ, Med Fak Mannheim, Med Klin 3, Mannheim, Germany

[2] Univ Munich, IBE, Munich, Germany

[3] Univ Klinikum, Med Klin 5, Erlangen, Germany

[4] Univ Munich, Med Klin 3, Munich, Germany

[5] Univ Klinikum, Klin Innere Med, Marburg, Germany

[6] Univ Klinikum Eppendorf, Med Klin 2, Hamburg, Germany

[7] Klinikum Schwabing, Munich, Germany

[8] Univ Spital, Basel, Switzerland

[9] Inselspital Bern, Bern, Switzerland

[10] Rhein Westfal TH Aachen, Aachen, Germany

[11] MLL, Munich, Germany

[12] MHH, Inst Humangenet, Hannover, Germany

[13] Ev Krankenhaus, Hamm, Germany

[14] Univ Klinikum, Med Klin & Poliklin, Wurzburg, Germany

[15] Klin Innere Med 3, Chemnitz, Germany

[16] Heidelberg Univ, Med Klin 5, Heidelberg, Germany

[17] Onkol Schwerpunktpraxis, Heilbronn, Germany

[18] Klinikum Nurnberg Nord, Med Klin 5, Nurnberg, Germany

[19] Univ Klinikum, Med Abt 2, Tubingen, Germany

[20] Caritas Krankenhaus, Lebach, Germany

[21] Univ Klinikum Schleswig Holstein, Med Klin & Poliklin 2, Kiel, Germany

[22] Univ Klinikum, Klin Innere Med 3, Ulm, Germany

[23] Klin Onkol & Hamatol, Oldenburg, Germany

[24] St Marien Hosp, Hagen, Germany

[25] Univ Klinikum, Med Klin 1, Freiburg, Germany

[26] Univ Saarland, Klin Innere Med 1, Homburg, Germany

[27] Univ Klinikum, Med Klin A, Munster, Germany

[28] Onkol Leer UnterEms, Leer, Germany

[29] Univ Klinikum, Klin & Poliklin Innere Med 3, Regensburg, Germany

[30] Masaryk Univ Hosp, Brno, Czech Republic

[31] Klin Knochenmarktransplantat, Essen, Germany

[32] Stadt Klinikum, Med Klin 3, Karlsruhe, Germany

[33] Westpfalz Klinikum, Klin Innere Med 3, Kaiserslautern, Germany

[34] Klinikum Bremen Mitte, Med Klin 1, Bremen, Germany

[35] Kantonsspital, Aarau, Switzerland

[36] St Antonius Hosp, Eschweiler, Germany

[37] Hamatol Onkolog Schwerpunktpraxis, Wurzburg, Germany

[38] Vivantes Klinikum Neukolln, Berlin, Germany

[39] Univ Med, Klin Hamatol & Med Onkol, Gottingen, Germany

[40] Stauferklinikum Schwabisch Gmund, Mutlangen, Germany

[41] Onkol Zentrum, Ansbach, Germany

[42] Praxisklin Hamatol & Onkol, Koblenz, Germany

[43] Univ Klinikum, Klin Innere Med 1, Cologne, Germany

[44] Ambulante Hamatol & Onkol, Bonn, Germany

[45] Internist Schwerpunktpraxis, Erlangen, Germany

[46] St Marien Krankenhaus, Siegen, Germany

[47] Charite, Berlin, Germany

[48] Barmherzige Bruder, Regensburg, Germany

[49] Univ, Med Klin 3, Bonn, Germany

[50] Diakonie, Schwabisch Hall, Germany

来源：

LEUKEMIA | 2017年 / 31卷 / 11期

关键词：

KINASE INHIBITOR OPTIMIZATION; MOLECULAR RESPONSE; 800; MG; EXPERT PANEL; END-POINTS; OPEN-LABEL; RECOMMENDATIONS; INTERFERON; PROGNOSIS; RISK;

D O I：

10.1038/leu.2017.253

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n = 400) could be optimized by doubling the dose (n = 420), adding interferon (IFN) (n = 430) or cytarabine (n = 158) or using IM after IFN-failure (n = 128). 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. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg 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, more life-time can currently be gained by carefully addressing non-CML determinants of survival.

引用

页码：2398 / 2406

页数：9

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