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1000 Titel
  • Expert opinion—management of chronic myeloid leukemia after resistance to second-generation tyrosine kinase inhibitors
1000 Autor/in
  1. Hochhaus, Andreas |
  2. Breccia, Massimo |
  3. Saglio, Giuseppe |
  4. García-Gutiérrez, Valentín |
  5. Réa, Delphine |
  6. Janssen, Jeroen |
  7. Apperley, Jane |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-05-04
1000 Erschienen in
1000 Quellenangabe
  • 34(6):1495-1502
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41375-020-0842-9 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266739/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Regardless of line of therapy, treatment goals in chronic phase chronic myeloid leukemia (CML) are: avoid progression to accelerated phase or blast crisis CML such that patients achieve a life expectancy comparable with that of the general population; avoid adverse events (AEs); and restore and maintain quality of life. The most important prognostic factor for achieving these goals is response to tyrosine kinase inhibitors (TKIs) at key milestones. For patients failing a TKI, a treatment change is mandatory to limit the risk of progression and death. There is currently no precise guideline for patients that fail a second-generation TKI, and there is a paucity of data to guide clinical decision making in this setting. There is, therefore, an unmet need for practical and actionable guidance on how to manage patients who fail a second-generation TKI. Although the term 'failure' includes patients failing for resistance or intolerance, the focus of this paper is failure of a second-generation TKI because of resistance. CML patients who fail their first second-generation TKI for true resistance need a more potent therapy. In these patients, the key issues to consider are the relative appropriateness of early allogeneic hematopoietic stem cell transplantation or the use of a further TKI. Selection of the next line of treatment after second-generation TKI resistance should be individualized and must be based on patient-specific factors including cytogenetics, mutation profile, comorbidities, age, previous history of AEs with prior TKI therapy, and risk profile for AEs on specific TKIs. This expert opinion paper is not in conflict with existing recommendations, but instead represents an evolution of previous notions, based on new data, insights, and clinical experience. We review the treatment options for patients resistant to second-generation TKI therapy and provide our clinical opinions and guidance on key considerations for treatment decision making.
1000 Sacherschließung
lokal Clinical trials
lokal Chronic myeloid leukaemia
lokal Humans [MeSH]
lokal Antineoplastic Agents/therapeutic use [MeSH]
lokal Review Article
lokal Protein Kinase Inhibitors/therapeutic use [MeSH]
lokal Drug Resistance, Neoplasm [MeSH]
lokal Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy [MeSH]
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