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

J 2017

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

HEHLMANN, R., M. LAUSEKER, S. SAUSSELE, M. PFIRRMANN, S. KRAUSE et. al.

Basic information

Original name

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

Authors

HEHLMANN, R. (276 Germany), M. LAUSEKER (276 Germany), S. SAUSSELE (276 Germany), M. PFIRRMANN (276 Germany), S. KRAUSE (276 Germany), H.J. KOLB (276 Germany), A. NEUBAUER (276 Germany), D.K. HOSSFELD (276 Germany), C. NERL (276 Germany), A. GRATWOHL (756 Switzerland), G.M. BAERLOCHER (756 Switzerland), D. HEIM (756 Switzerland), T.H. BRUMMENDORF (276 Germany), A. FABARIUS (276 Germany), C. HAFERLACH (276 Germany), B. SCHLEGELBERGER (276 Germany), M.C. MULLER (276 Germany), S. JEROMIN (276 Germany), U. PROETEL (276 Germany), K. KOHLBRENNER (276 Germany), A. VOSKANYAN (276 Germany), S. RINALDETTI (276 Germany), W. SEIFARTH (276 Germany), B. SPIESS (276 Germany), L. BALLEISEN (276 Germany), M.C. GOEBELER (276 Germany), M. HANEL (276 Germany), A. HO (276 Germany), J. DENGLER (276 Germany), C. FALGE (276 Germany), L. KANZ (276 Germany), S. KREMERS (276 Germany), A. BURCHERT (276 Germany), M. KNEBA (276 Germany), F. STEGELMANN (276 Germany), C.A. KOHNE (276 Germany), H.W. LINDEMANN (276 Germany), C.F. WALLER (276 Germany), M. PFREUNDSCHUH (276 Germany), K. SPIEKERMANN (276 Germany), W.E. BERDEL (276 Germany), L. MULLER (276 Germany), M. EDINGER (276 Germany), Jiří MAYER (203 Czech Republic, guarantor, belonging to the institution), D.W. BEELEN (276 Germany), M. BENTZ (276 Germany), H. LINK (276 Germany), B. HERTENSTEIN (276 Germany), R. FUCHS (276 Germany), M. WERNLI (756 Switzerland), F. SCHLEGEL (276 Germany), R. SCHLAG (276 Germany), M.de WIT (276 Germany), L. TRUMPER (276 Germany), H. HEBART (276 Germany), M. HAHN (276 Germany), J. THOMALLA (276 Germany), C. SCHEID (276 Germany), P. SCHAFHAUSEN (276 Germany), W. VERBEEK (276 Germany), M.J. ECKART (276 Germany), W. GASSMANN (276 Germany), A.. PEZZUTTO (276 Germany), M. SCHENK (276 Germany), P. BROSSART (276 Germany), T. GEER (276 Germany), S. BILDAT (276 Germany), E. SCHAFER (276 Germany), A. HOCHHAUS (276 Germany) and J. HASFORD (276 Germany)

Edition

Leukemia, London, Nature Publishing Group, 2017, 0887-6924

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 10.023

RIV identification code

RIV/00216224:14110/17:00100053

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1038/leu.2017.253

UT WoS

000414215400013

Keywords in English

chronic myeloid leukemia; imatinib

Abstract

V originále

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.

Citovat

HEHLMANN, R., M. LAUSEKER, S. SAUSSELE, M. PFIRRMANN, S. KRAUSE, H.J. KOLB, A. NEUBAUER, D.K. HOSSFELD, C. NERL, A. GRATWOHL, G.M. BAERLOCHER, D. HEIM, T.H. BRUMMENDORF, A. FABARIUS, C. HAFERLACH, B. SCHLEGELBERGER, M.C. MULLER, S. JEROMIN, U. PROETEL, K. KOHLBRENNER, A. VOSKANYAN, S. RINALDETTI, W. SEIFARTH, B. SPIESS, L. BALLEISEN, M.C. GOEBELER, M. HANEL, A. HO, J. DENGLER, C. FALGE, L. KANZ, S. KREMERS, A. BURCHERT, M. KNEBA, F. STEGELMANN, C.A. KOHNE, H.W. LINDEMANN, C.F. WALLER, M. PFREUNDSCHUH, K. SPIEKERMANN, W.E. BERDEL, L. MULLER, M. EDINGER, Jiří MAYER, D.W. BEELEN, M. BENTZ, H. LINK, B. HERTENSTEIN, R. FUCHS, M. WERNLI, F. SCHLEGEL, R. SCHLAG, M.de WIT, L. TRUMPER, H. HEBART, M. HAHN, J. THOMALLA, C. SCHEID, P. SCHAFHAUSEN, W. VERBEEK, M.J. ECKART, W. GASSMANN, A.. PEZZUTTO, M. SCHENK, P. BROSSART, T. GEER, S. BILDAT, E. SCHAFER, A. HOCHHAUS and J. HASFORD. 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. Leukemia. London: Nature Publishing Group, 2017, vol. 31, No 11, p. 2398-2406. ISSN 0887-6924. Available from: https://dx.doi.org/10.1038/leu.2017.253.

@article{1408665,
   author = {Hehlmann, R. and Lauseker, M. and Saussele, S. and Pfirrmann, M. and Krause, S. and Kolb, H.J. and Neubauer, A. and Hossfeld, D.K. and Nerl, C. and Gratwohl, A. and Baerlocher, G.M. and Heim, D. and Brummendorf, T.H. and Fabarius, A. and Haferlach, C. and Schlegelberger, B. and Muller, M.C. and Jeromin, S. and Proetel, U. and Kohlbrenner, K. and Voskanyan, A. and Rinaldetti, S. and Seifarth, W. and Spiess, B. and Balleisen, L. and Goebeler, M.C. and Hanel, M. and Ho, A. and Dengler, J. and Falge, C. and Kanz, L. and Kremers, S. and Burchert, A. and Kneba, M. and Stegelmann, F. and Kohne, C.A. and Lindemann, H.W. and Waller, C.F. and Pfreundschuh, M. and Spiekermann, K. and Berdel, W.E. and Muller, L. and Edinger, M. and Mayer, Jiří and Beelen, D.W. and Bentz, M. and Link, H. and Hertenstein, B. and Fuchs, R. and Wernli, M. and Schlegel, F. and Schlag, R. and Wit, M.de and Trumper, L. and Hebart, H. and Hahn, M. and Thomalla, J. and Scheid, C. and Schafhausen, P. and Verbeek, W. and Eckart, M.J. and Gassmann, W. and Pezzutto, A.. and Schenk, M. and Brossart, P. and Geer, T. and Bildat, S. and Schafer, E. and Hochhaus, A. and Hasford, J.},
   article_location = {London},
   article_number = {11},
   doi = {http://dx.doi.org/10.1038/leu.2017.253},
   keywords = {chronic myeloid leukemia; imatinib},
   language = {eng},
   issn = {0887-6924},
   journal = {Leukemia},
   title = {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},
   volume = {31},
   year = {2017}
}

TY  - JOUR
ID  - 1408665
AU  - Hehlmann, R. - Lauseker, M. - Saussele, S. - Pfirrmann, M. - Krause, S. - Kolb, H.J. - Neubauer, A. - Hossfeld, D.K. - Nerl, C. - Gratwohl, A. - Baerlocher, G.M. - Heim, D. - Brummendorf, T.H. - Fabarius, A. - Haferlach, C. - Schlegelberger, B. - Muller, M.C. - Jeromin, S. - Proetel, U. - Kohlbrenner, K. - Voskanyan, A. - Rinaldetti, S. - Seifarth, W. - Spiess, B. - Balleisen, L. - Goebeler, M.C. - Hanel, M. - Ho, A. - Dengler, J. - Falge, C. - Kanz, L. - Kremers, S. - Burchert, A. - Kneba, M. - Stegelmann, F. - Kohne, C.A. - Lindemann, H.W. - Waller, C.F. - Pfreundschuh, M. - Spiekermann, K. - Berdel, W.E. - Muller, L. - Edinger, M. - Mayer, Jiří - Beelen, D.W. - Bentz, M. - Link, H. - Hertenstein, B. - Fuchs, R. - Wernli, M. - Schlegel, F. - Schlag, R. - Wit, M.de - Trumper, L. - Hebart, H. - Hahn, M. - Thomalla, J. - Scheid, C. - Schafhausen, P. - Verbeek, W. - Eckart, M.J. - Gassmann, W. - Pezzutto, A.. - Schenk, M. - Brossart, P. - Geer, T. - Bildat, S. - Schafer, E. - Hochhaus, A. - Hasford, J.
PY  - 2017
TI  - 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
JF  - Leukemia
VL  - 31
IS  - 11
SP  - 2398-2406
EP  - 2398-2406
PB  - Nature Publishing Group
SN  - 08876924
KW  - chronic myeloid leukemia
KW  - imatinib
N2  - 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.
ER  -

HEHLMANN, R., M. LAUSEKER, S. SAUSSELE, M. PFIRRMANN, S. KRAUSE, H.J. KOLB, A. NEUBAUER, D.K. HOSSFELD, C. NERL, A. GRATWOHL, G.M. BAERLOCHER, D. HEIM, T.H. BRUMMENDORF, A. FABARIUS, C. HAFERLACH, B. SCHLEGELBERGER, M.C. MULLER, S. JEROMIN, U. PROETEL, K. KOHLBRENNER, A. VOSKANYAN, S. RINALDETTI, W. SEIFARTH, B. SPIESS, L. BALLEISEN, M.C. GOEBELER, M. HANEL, A. HO, J. DENGLER, C. FALGE, L. KANZ, S. KREMERS, A. BURCHERT, M. KNEBA, F. STEGELMANN, C.A. KOHNE, H.W. LINDEMANN, C.F. WALLER, M. PFREUNDSCHUH, K. SPIEKERMANN, W.E. BERDEL, L. MULLER, M. EDINGER, Jiří MAYER, D.W. BEELEN, M. BENTZ, H. LINK, B. HERTENSTEIN, R. FUCHS, M. WERNLI, F. SCHLEGEL, R. SCHLAG, M.de WIT, L. TRUMPER, H. HEBART, M. HAHN, J. THOMALLA, C. SCHEID, P. SCHAFHAUSEN, W. VERBEEK, M.J. ECKART, W. GASSMANN, A.. PEZZUTTO, M. SCHENK, P. BROSSART, T. GEER, S. BILDAT, E. SCHAFER, A. HOCHHAUS and J. HASFORD. 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. \textit{Leukemia}. London: Nature Publishing Group, 2017, vol.~31, No~11, p.~2398-2406. ISSN~0887-6924. Available from: https://dx.doi.org/10.1038/leu.2017.253.

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