Results of the European survey on the assessment of deep molecular response in chronic phase CML patients during tyrosine kinase inhibitor therapy (EUREKA registry).

Autor: Möbius S; Abteilung Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Am Klinikum 1, 07740, Jena, Germany., Schenk T; Abteilung Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Am Klinikum 1, 07740, Jena, Germany., Himsel D; Abteilung Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Am Klinikum 1, 07740, Jena, Germany., Maier J; Abteilung für Hämatologie und internistische Onkologie, Universität Leipzig, Leipzig, Germany., Franke GN; Abteilung für Hämatologie und internistische Onkologie, Universität Leipzig, Leipzig, Germany., Saussele S; III. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany., Pott C; Second Medical Department, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany., Andrikovics H; National Blood Service, Budapest, Hungary.; Central Hospital of Southern Pest, Budapest, Hungary., Meggyesi N; National Blood Service, Budapest, Hungary.; Central Hospital of Southern Pest, Budapest, Hungary., Machova-Polakova K; Department of Molecular Genetics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic., Zizkova H; Department of Molecular Genetics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic., Jurcek T; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.; Faculty of Medicine, Masaryk University Brno, Brno, Czech Republic., Mesanovic S; Pathology Department, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina., Zadro R; University Hospital Center Zagreb, University of Zagreb, Faculty of Pharmacy and Biochemistry, Zagreb, Croatia., Gottardi E; Division of Internal Medicine and Hematology, University of Turin, Orbassano, Italy., Haenig J; Novartis Oncology, Global Medical Affairs, Basel, Switzerland., Schuld P; Novartis Oncology, Global Medical Affairs, Basel, Switzerland., Cross NCP; Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury, UK.; Faculty of Medicine, University of Southampton, Southampton, UK., Hochhaus A; Abteilung Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Am Klinikum 1, 07740, Jena, Germany., Ernst T; Abteilung Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Am Klinikum 1, 07740, Jena, Germany. thomas.ernst@med.uni-jena.de.
Jazyk: angličtina
Zdroj: Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2019 Jun; Vol. 145 (6), pp. 1645-1650. Date of Electronic Publication: 2019 Apr 02.
DOI: 10.1007/s00432-019-02910-6
Abstrakt: Purpose: The advent of tyrosine kinase inhibitor (TKI) therapies has revolutionized the treatment of chronic myeloid leukemia (CML). The European LeukemiaNet (ELN) recommends quantification of BCR-ABL1 transcripts by real-time quantitative PCR every 3 months during TKI treatment. Since a proportion of patients in deep molecular response (DMR: MR 4 , MR 4.5 , MR 5 ) maintain remission after treatment stop, assessment of DMR is crucial. However, systematically collected molecular data, monitored with sensitive standardized assays, are not available outside clinical trials.
Methods: Data were collected on the standardized assessment of molecular response in the context of real-life practice. BCR-ABL1 transcript levels after > 2 years of TKI therapy were evaluated for DMR by local laboratories as well as standardized EUTOS laboratories. Since standardized molecular monitoring is a prerequisite for treatment discontinuation, central surveillance of the performance of the participating laboratories was carried out.
Results: Between 2014 and 2017, 3377 peripheral blood samples from 1117 CML patients were shipped to 11 standardized reference laboratories in six European countries. BCR-ABL1 transcript types were b3a2 (41.63%), b2a2 (29.99%), b2a2/b3a2 (3.58%) and atypical (0.54%). For 23.72% of the patients, the initial transcript type had not been reported. Response levels (EUTOS laboratory) were: no MMR, n = 197 (6.51%); MMR, n = 496 (16.40%); MR 4 , n = 685 (22.64%); MR 4.5 , n = 937 (30.98%); MR 5 , n = 710 (23.47%). With a Cohen's kappa coefficient of 0.708, a substantial agreement between EUTOS-certified and local laboratories was shown.
Conclusions: Multicenter DMR assessment is feasible in the context of real-life clinical practice in Europe. Information on the BCR-ABL1 transcript type at diagnosis is crucial to accurately monitor patients' molecular response during or after TKI therapy.
Databáze: MEDLINE
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