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Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV

Major molecular remission (MMR) is an important therapy goal in chronic myeloid leukemia (CML). So far, MMR is not a failure criterion according to ELN management recommendation leading to uncertainties when to change therapy in CML patients not reaching MMR after 12 months. At monthly landmarks, fo...

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Autores principales: Saussele, Susanne, Hehlmann, Rüdiger, Fabarius, Alice, Jeromin, Sabine, Proetel, Ulrike, Rinaldetti, Sebastien, Kohlbrenner, Katharina, Einsele, Hermann, Falge, Christiane, Kanz, Lothar, Neubauer, Andreas, Kneba, Michael, Stegelmann, Frank, Pfreundschuh, Michael, Waller, Cornelius F., Oppliger Leibundgut, Elisabeth, Heim, Dominik, Krause, Stefan W., Hofmann, Wolf-Karsten, Hasford, Joerg, Pfirrmann, Markus, Müller, Martin C., Hochhaus, Andreas, Lauseker, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940636/
https://www.ncbi.nlm.nih.gov/pubmed/29479070
http://dx.doi.org/10.1038/s41375-018-0055-7
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author Saussele, Susanne
Hehlmann, Rüdiger
Fabarius, Alice
Jeromin, Sabine
Proetel, Ulrike
Rinaldetti, Sebastien
Kohlbrenner, Katharina
Einsele, Hermann
Falge, Christiane
Kanz, Lothar
Neubauer, Andreas
Kneba, Michael
Stegelmann, Frank
Pfreundschuh, Michael
Waller, Cornelius F.
Oppliger Leibundgut, Elisabeth
Heim, Dominik
Krause, Stefan W.
Hofmann, Wolf-Karsten
Hasford, Joerg
Pfirrmann, Markus
Müller, Martin C.
Hochhaus, Andreas
Lauseker, Michael
author_facet Saussele, Susanne
Hehlmann, Rüdiger
Fabarius, Alice
Jeromin, Sabine
Proetel, Ulrike
Rinaldetti, Sebastien
Kohlbrenner, Katharina
Einsele, Hermann
Falge, Christiane
Kanz, Lothar
Neubauer, Andreas
Kneba, Michael
Stegelmann, Frank
Pfreundschuh, Michael
Waller, Cornelius F.
Oppliger Leibundgut, Elisabeth
Heim, Dominik
Krause, Stefan W.
Hofmann, Wolf-Karsten
Hasford, Joerg
Pfirrmann, Markus
Müller, Martin C.
Hochhaus, Andreas
Lauseker, Michael
author_sort Saussele, Susanne
collection PubMed
description Major molecular remission (MMR) is an important therapy goal in chronic myeloid leukemia (CML). So far, MMR is not a failure criterion according to ELN management recommendation leading to uncertainties when to change therapy in CML patients not reaching MMR after 12 months. At monthly landmarks, for different molecular remission status Hazard ratios (HR) were estimated for patients registered to CML study IV who were divided in a learning and a validation sample. The minimum HR for MMR was found at 2.5 years with 0.28 (compared to patients without remission). In the validation sample, a significant advantage for progression-free survival (PFS) for patients in MMR could be detected (p-value 0.007). The optimal time to predict PFS in patients with MMR could be validated in an independent sample at 2.5 years. With our model we provide a suggestion when to define lack of MMR as therapy failure and thus treatment change should be considered. The optimal response time for 1% BCR-ABL at about 12–15 months was confirmed and for deep molecular remission no specific time point was detected. Nevertheless, it was demonstrated that the earlier the MMR is achieved the higher is the chance to attain deep molecular response later.
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spelling pubmed-59406362018-05-10 Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV Saussele, Susanne Hehlmann, Rüdiger Fabarius, Alice Jeromin, Sabine Proetel, Ulrike Rinaldetti, Sebastien Kohlbrenner, Katharina Einsele, Hermann Falge, Christiane Kanz, Lothar Neubauer, Andreas Kneba, Michael Stegelmann, Frank Pfreundschuh, Michael Waller, Cornelius F. Oppliger Leibundgut, Elisabeth Heim, Dominik Krause, Stefan W. Hofmann, Wolf-Karsten Hasford, Joerg Pfirrmann, Markus Müller, Martin C. Hochhaus, Andreas Lauseker, Michael Leukemia Article Major molecular remission (MMR) is an important therapy goal in chronic myeloid leukemia (CML). So far, MMR is not a failure criterion according to ELN management recommendation leading to uncertainties when to change therapy in CML patients not reaching MMR after 12 months. At monthly landmarks, for different molecular remission status Hazard ratios (HR) were estimated for patients registered to CML study IV who were divided in a learning and a validation sample. The minimum HR for MMR was found at 2.5 years with 0.28 (compared to patients without remission). In the validation sample, a significant advantage for progression-free survival (PFS) for patients in MMR could be detected (p-value 0.007). The optimal time to predict PFS in patients with MMR could be validated in an independent sample at 2.5 years. With our model we provide a suggestion when to define lack of MMR as therapy failure and thus treatment change should be considered. The optimal response time for 1% BCR-ABL at about 12–15 months was confirmed and for deep molecular remission no specific time point was detected. Nevertheless, it was demonstrated that the earlier the MMR is achieved the higher is the chance to attain deep molecular response later. Nature Publishing Group UK 2018-02-26 2018 /pmc/articles/PMC5940636/ /pubmed/29479070 http://dx.doi.org/10.1038/s41375-018-0055-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. If you remix, transform, or build upon this article or a part thereof, you must distribute your contributions under the same license as the original. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/.
spellingShingle Article
Saussele, Susanne
Hehlmann, Rüdiger
Fabarius, Alice
Jeromin, Sabine
Proetel, Ulrike
Rinaldetti, Sebastien
Kohlbrenner, Katharina
Einsele, Hermann
Falge, Christiane
Kanz, Lothar
Neubauer, Andreas
Kneba, Michael
Stegelmann, Frank
Pfreundschuh, Michael
Waller, Cornelius F.
Oppliger Leibundgut, Elisabeth
Heim, Dominik
Krause, Stefan W.
Hofmann, Wolf-Karsten
Hasford, Joerg
Pfirrmann, Markus
Müller, Martin C.
Hochhaus, Andreas
Lauseker, Michael
Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV
title Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV
title_full Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV
title_fullStr Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV
title_full_unstemmed Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV
title_short Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV
title_sort defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized cml study iv
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940636/
https://www.ncbi.nlm.nih.gov/pubmed/29479070
http://dx.doi.org/10.1038/s41375-018-0055-7
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