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Current Treatment Options for Chronic Myeloid Leukemia Patients Failing Second-Generation Tyrosine Kinase Inhibitors.

ABSTRACT: Despite the excellent overall survival (OS) of patients with chronic myeloid leukemia (CML), a significant proportion will not achieve optimal response to imatinib or second-generation tyrosine kinase inhibitors (2GTKI). For patients with inadequate response to 2GTKIs, alternative 2GTKIs or ponatinib are widely available treatment options in daily clinical practice. Treatment decisions should be guided by correct identification of the cause of treatment failure and accurate distinction between resistant from intolerant or nonadherence patients. This review aims to provide practical advice on how to select the best treatment option in each clinical scenario.

SUBMITTER: Garcia-Gutierrez V

PROVIDER: S-EPMC7408792 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Current Treatment Options for Chronic Myeloid Leukemia Patients Failing Second-Generation Tyrosine Kinase Inhibitors.

García-Gutiérrez Valentín V Hernández-Boluda Juan Carlos Carlos JCC

Journal of clinical medicine 20200715 7

Despite the excellent overall survival (OS) of patients with chronic myeloid leukemia (CML), a significant proportion will not achieve optimal response to imatinib or second-generation tyrosine kinase inhibitors (2GTKI). For patients with inadequate response to 2GTKIs, alternative 2GTKIs or ponatinib are widely available treatment options in daily clinical practice. Treatment decisions should be guided by correct identification of the cause of treatment failure and accurate distinction between r ...[more]

PMID: 32679880

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Project description: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.

Dataset Information

Current Treatment Options for Chronic Myeloid Leukemia Patients Failing Second-Generation Tyrosine Kinase Inhibitors.

Publications

Current Treatment Options for Chronic Myeloid Leukemia Patients Failing Second-Generation Tyrosine Kinase Inhibitors.

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