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Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV
Standard first-line therapy of chronic myeloid leukemia is treatment with imatinib. In the randomized German Chronic Myeloid Leukemia-Study IV, more potent BCR-ABL inhibition with 800 mg (‘high-dose’) imatinib accelerated achievement of a deep molecular remission. However, whether and when a de-esca...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ferrata Storti Foundation
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518910/ https://www.ncbi.nlm.nih.gov/pubmed/30514803 http://dx.doi.org/10.3324/haematol.2018.206797 |
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author | Michel, Christian Burchert, Andreas Hochhaus, Andreas Saussele, Susanne Neubauer, Andreas Lauseker, Michael Krause, Stefan W. Kolb, Hans-Jochem Hossfeld, Dieter Kurt Nerl, Christoph Baerlocher, Gabriela M. Heim, Dominik Brümmendorf, Tim H Fabarius, Alice Haferlach, Claudia Schlegelberger, Brigitte Balleisen, Leopold Goebeler, Maria-Elisabeth Hänel, Mathias Ho, Anthony Dengler, Jolanta Falge, Christiane Möhle, Robert Kremers, Stephan Kneba, Michael Stegelmann, Frank Köhne, Claus-Henning Lindemann, Hans-Walter Waller, Cornelius F. Spiekermann, Karsten Berdel, Wolfgang E. Müller, Lothar Edinger, Matthias Mayer, Jiri Beelen, Dietrich W. Bentz, Martin Link, Hartmut Hertenstein, Bernd Fuchs, Roland Wernli, Martin Schlegel, Frank Schlag, Rudolf de Wit, Maike Trümper, Lorenz Hebart, Holger Hahn, Markus Thomalla, Jörg Scheid, Christof Schafhausen, Philippe Verbeek, Walter Eckart, Michael J. Gassmann, Winfried Schenk, Michael Brossart, Peter Wündisch, Thomas Geer, Thomas Bildat, Stephan Schäfer, Erhardt Hasford, Joerg Hehlmann, Rüdiger Pfirrmann, Markus |
author_facet | Michel, Christian Burchert, Andreas Hochhaus, Andreas Saussele, Susanne Neubauer, Andreas Lauseker, Michael Krause, Stefan W. Kolb, Hans-Jochem Hossfeld, Dieter Kurt Nerl, Christoph Baerlocher, Gabriela M. Heim, Dominik Brümmendorf, Tim H Fabarius, Alice Haferlach, Claudia Schlegelberger, Brigitte Balleisen, Leopold Goebeler, Maria-Elisabeth Hänel, Mathias Ho, Anthony Dengler, Jolanta Falge, Christiane Möhle, Robert Kremers, Stephan Kneba, Michael Stegelmann, Frank Köhne, Claus-Henning Lindemann, Hans-Walter Waller, Cornelius F. Spiekermann, Karsten Berdel, Wolfgang E. Müller, Lothar Edinger, Matthias Mayer, Jiri Beelen, Dietrich W. Bentz, Martin Link, Hartmut Hertenstein, Bernd Fuchs, Roland Wernli, Martin Schlegel, Frank Schlag, Rudolf de Wit, Maike Trümper, Lorenz Hebart, Holger Hahn, Markus Thomalla, Jörg Scheid, Christof Schafhausen, Philippe Verbeek, Walter Eckart, Michael J. Gassmann, Winfried Schenk, Michael Brossart, Peter Wündisch, Thomas Geer, Thomas Bildat, Stephan Schäfer, Erhardt Hasford, Joerg Hehlmann, Rüdiger Pfirrmann, Markus |
author_sort | Michel, Christian |
collection | PubMed |
description | Standard first-line therapy of chronic myeloid leukemia is treatment with imatinib. In the randomized German Chronic Myeloid Leukemia-Study IV, more potent BCR-ABL inhibition with 800 mg (‘high-dose’) imatinib accelerated achievement of a deep molecular remission. However, whether and when a de-escalation of the dose intensity under high-dose imatinib can be safely performed without increasing the risk of losing deep molecular response is unknown. To gain insights into this clinically relevant question, we analyzed the outcome of imatinib dose reductions from 800 mg to 400 mg daily in the Chronic Myeloid Leukemia-Study IV. Of the 422 patients that were randomized to the 800 mg arm, 68 reduced imatinib to 400 mg after they had achieved at least a stable major molecular response. Of these 68 patients, 61 (90%) maintained major molecular remission on imatinib at 400 mg. Five of the seven patients who lost major molecular remission on the imatinib standard dose regained major molecular remission while still on 400 mg imatinib. Only two of 68 patients had to switch to more potent kinase inhibition to regain major molecular remission. Importantly, the lengths of the intervals between imatinib high-dose treatment before and after achieving major molecular remission were associated with the probabilities of maintaining major molecular remission with the standard dose of imatinib. Taken together, the data support the view that a deep molecular remission achieved with high-dose imatinib can be safely maintained with standard dose in most patients. Study protocol registered at clinicaltrials.gov 00055874. |
format | Online Article Text |
id | pubmed-6518910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Ferrata Storti Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-65189102019-05-24 Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV Michel, Christian Burchert, Andreas Hochhaus, Andreas Saussele, Susanne Neubauer, Andreas Lauseker, Michael Krause, Stefan W. Kolb, Hans-Jochem Hossfeld, Dieter Kurt Nerl, Christoph Baerlocher, Gabriela M. Heim, Dominik Brümmendorf, Tim H Fabarius, Alice Haferlach, Claudia Schlegelberger, Brigitte Balleisen, Leopold Goebeler, Maria-Elisabeth Hänel, Mathias Ho, Anthony Dengler, Jolanta Falge, Christiane Möhle, Robert Kremers, Stephan Kneba, Michael Stegelmann, Frank Köhne, Claus-Henning Lindemann, Hans-Walter Waller, Cornelius F. Spiekermann, Karsten Berdel, Wolfgang E. Müller, Lothar Edinger, Matthias Mayer, Jiri Beelen, Dietrich W. Bentz, Martin Link, Hartmut Hertenstein, Bernd Fuchs, Roland Wernli, Martin Schlegel, Frank Schlag, Rudolf de Wit, Maike Trümper, Lorenz Hebart, Holger Hahn, Markus Thomalla, Jörg Scheid, Christof Schafhausen, Philippe Verbeek, Walter Eckart, Michael J. Gassmann, Winfried Schenk, Michael Brossart, Peter Wündisch, Thomas Geer, Thomas Bildat, Stephan Schäfer, Erhardt Hasford, Joerg Hehlmann, Rüdiger Pfirrmann, Markus Haematologica Article Standard first-line therapy of chronic myeloid leukemia is treatment with imatinib. In the randomized German Chronic Myeloid Leukemia-Study IV, more potent BCR-ABL inhibition with 800 mg (‘high-dose’) imatinib accelerated achievement of a deep molecular remission. However, whether and when a de-escalation of the dose intensity under high-dose imatinib can be safely performed without increasing the risk of losing deep molecular response is unknown. To gain insights into this clinically relevant question, we analyzed the outcome of imatinib dose reductions from 800 mg to 400 mg daily in the Chronic Myeloid Leukemia-Study IV. Of the 422 patients that were randomized to the 800 mg arm, 68 reduced imatinib to 400 mg after they had achieved at least a stable major molecular response. Of these 68 patients, 61 (90%) maintained major molecular remission on imatinib at 400 mg. Five of the seven patients who lost major molecular remission on the imatinib standard dose regained major molecular remission while still on 400 mg imatinib. Only two of 68 patients had to switch to more potent kinase inhibition to regain major molecular remission. Importantly, the lengths of the intervals between imatinib high-dose treatment before and after achieving major molecular remission were associated with the probabilities of maintaining major molecular remission with the standard dose of imatinib. Taken together, the data support the view that a deep molecular remission achieved with high-dose imatinib can be safely maintained with standard dose in most patients. Study protocol registered at clinicaltrials.gov 00055874. Ferrata Storti Foundation 2019-05 /pmc/articles/PMC6518910/ /pubmed/30514803 http://dx.doi.org/10.3324/haematol.2018.206797 Text en Copyright© 2019 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher. |
spellingShingle | Article Michel, Christian Burchert, Andreas Hochhaus, Andreas Saussele, Susanne Neubauer, Andreas Lauseker, Michael Krause, Stefan W. Kolb, Hans-Jochem Hossfeld, Dieter Kurt Nerl, Christoph Baerlocher, Gabriela M. Heim, Dominik Brümmendorf, Tim H Fabarius, Alice Haferlach, Claudia Schlegelberger, Brigitte Balleisen, Leopold Goebeler, Maria-Elisabeth Hänel, Mathias Ho, Anthony Dengler, Jolanta Falge, Christiane Möhle, Robert Kremers, Stephan Kneba, Michael Stegelmann, Frank Köhne, Claus-Henning Lindemann, Hans-Walter Waller, Cornelius F. Spiekermann, Karsten Berdel, Wolfgang E. Müller, Lothar Edinger, Matthias Mayer, Jiri Beelen, Dietrich W. Bentz, Martin Link, Hartmut Hertenstein, Bernd Fuchs, Roland Wernli, Martin Schlegel, Frank Schlag, Rudolf de Wit, Maike Trümper, Lorenz Hebart, Holger Hahn, Markus Thomalla, Jörg Scheid, Christof Schafhausen, Philippe Verbeek, Walter Eckart, Michael J. Gassmann, Winfried Schenk, Michael Brossart, Peter Wündisch, Thomas Geer, Thomas Bildat, Stephan Schäfer, Erhardt Hasford, Joerg Hehlmann, Rüdiger Pfirrmann, Markus Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV |
title | Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV |
title_full | Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV |
title_fullStr | Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV |
title_full_unstemmed | Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV |
title_short | Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV |
title_sort | imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the german chronic myeloid leukemia-study iv |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518910/ https://www.ncbi.nlm.nih.gov/pubmed/30514803 http://dx.doi.org/10.3324/haematol.2018.206797 |
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