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Outcome after failure of second generation tyrosine kinase inhibitors treatment as first-line therapy for patients with chronic myeloid leukemia.

ABSTRACT: The outcome of patients with CML who discontinue 2G-TKI initial therapy is unknown. We analyzed the characteristics of patients in whom treatment with first-line 2G-TKIs had failed.A total of 218 patients with CML were treated with dasatinib (n = 101) or nilotinib (n = 117; 12 in AP). After a median follow-up of 23 months, 40 patients (18%) discontinued therapy: 25 initially treated with nilotinib (21% of all treated with nilotinib; 6 treated in AP) and 15 (15%) initially treated with dasatinib. Median age of the patients was 47 (range, 19-79) years, and they had received therapy for a median of 8 (range, 0-62) months.Reasons for treatment discontinuation include: toxicity, 16 patients; resistance in CP, 5 patients; transformation to blast phase, 4 patients (2 treated in AP); and other reasons, 15 patients. Subsequent treatment was imatinib in 11 patients, nilotinib in 7, dasatinib in 4, ponatinib in 2, chemotherapy plus dasatinib in 3, stem cell transplant in 2, bafetinib in 1, and unknown or none in 8 patients. A complete cytogenetic response was achieved in 19 patients, including 17 with major molecular response. Fourteen of the patients who achieved a complete molecular response or major molecular response with subsequent TKIs were in CP at the time of 2G-TKI discontinuation.We conclude that treatment failure after first-line therapy with 2G-TKIs is mostly associated with toxicity or patient preference, and these patients respond well to alternative TKIs.

SUBMITTER: Eghtedar A

PROVIDER: S-EPMC3752280 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Outcome after failure of second generation tyrosine kinase inhibitors treatment as first-line therapy for patients with chronic myeloid leukemia.

Eghtedar Alireza A Kantarjian Hagop H Jabbour Elias E O'Brien Susan S Burton Elizabeth E Garcia-Manero Guillermo G Verstovsek Srdan S Ravandi Farhad F Borthakur Gautam G Konopleva Marina M Quintas-Cardama Alfonso A Cortes Jorge J

Clinical lymphoma, myeloma & leukemia 20130614 4

<h4>Introduction</h4>The outcome of patients with CML who discontinue 2G-TKI initial therapy is unknown. We analyzed the characteristics of patients in whom treatment with first-line 2G-TKIs had failed.<h4>Patients and methods</h4>A total of 218 patients with CML were treated with dasatinib (n = 101) or nilotinib (n = 117; 12 in AP). After a median follow-up of 23 months, 40 patients (18%) discontinued therapy: 25 initially treated with nilotinib (21% of all treated with nilotinib; 6 treated in ...[more]

PMID: 23770156

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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.

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Outcome after failure of second generation tyrosine kinase inhibitors treatment as first-line therapy for patients with chronic myeloid leukemia.

Publications

Outcome after failure of second generation tyrosine kinase inhibitors treatment as first-line therapy for patients with chronic myeloid leukemia.

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