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Discontinuation of ...
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Saussele, SusanneHeidelberg University,Heidelberg Univ, Dept Haematol & Oncol, Univ Hosp Mannheim, Mannheim, Germany
(författare)
Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI) : a prespecified interim analysis of a prospective, multicentre, non-randomised, trial
- Artikel/kapitelEngelska2018
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Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:9c50c3dd-6929-400e-9e3f-ef22727d85d0
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https://lup.lub.lu.se/record/9c50c3dd-6929-400e-9e3f-ef22727d85d0URI
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https://doi.org/10.1016/S1470-2045(18)30192-XDOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-357715URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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Background: Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with chronic myeloid leukaemia. Many patients have deep molecular responses, a prerequisite for TKI therapy discontinuation. We aimed to define precise conditions for stopping treatment. Methods: In this prospective, non-randomised trial, we enrolled patients with chronic myeloid leukaemia at 61 European centres in 11 countries. Eligible patients had chronic-phase chronic myeloid leukaemia, had received any TKI for at least 3 years (without treatment failure according to European LeukemiaNet [ELN] recommendations), and had a confirmed deep molecular response for at least 1 year. The primary endpoint was molecular relapse-free survival, defined by loss of major molecular response (MMR; >0·1% BCR-ABL1 on the International Scale) and assessed in all patients with at least one molecular result. Secondary endpoints were a prognostic analysis of factors affecting maintenance of MMR at 6 months in learning and validation samples and the cost impact of stopping TKI therapy. We considered loss of haematological response, progress to accelerated-phase chronic myeloid leukaemia, or blast crisis as serious adverse events. This study presents the results of the prespecified interim analysis, which was done after the 6-month molecular relapse-free survival status was known for 200 patients. The study is ongoing and is registered with ClinicalTrials.gov, number NCT01596114. Findings: Between May 30, 2012, and Dec 3, 2014, we assessed 868 patients with chronic myeloid leukaemia for eligibility, of whom 758 were enrolled. Median follow-up of the 755 patients evaluable for molecular response was 27 months (IQR 21–34). Molecular relapse-free survival for these patients was 61% (95% CI 57–64) at 6 months and 50% (46–54) at 24 months. Of these 755 patients, 371 (49%) lost MMR after TKI discontinuation, four (1%) died while in MMR for reasons unrelated to chronic myeloid leukaemia (myocardial infarction, lung cancer, renal cancer, and heart failure), and 13 (2%) restarted TKI therapy while in MMR. A further six (1%) patients died in chronic-phase chronic myeloid leukaemia after loss of MMR and re-initiation of TKI therapy for reasons unrelated to chronic myeloid leukaemia, and two (<1%) patients lost MMR despite restarting TKI therapy. In the prognostic analysis in 405 patients who received imatinib as first-line treatment (learning sample), longer treatment duration (odds ratio [OR] per year 1·14 [95% CI 1·05–1·23]; p=0·0010) and longer deep molecular response durations (1·13 [1·04–1·23]; p=0·0032) were associated with increasing probability of MMR maintenance at 6 months. The OR for deep molecular response duration was replicated in the validation sample consisting of 171 patients treated with any TKI as first-line treatment, although the association was not significant (1·13 [0·98–1·29]; p=0·08). TKI discontinuation was associated with substantial cost savings (an estimated €22 million). No serious adverse events were reported. Interpretation: Patients with chronic myeloid leukaemia who have achieved deep molecular responses have good molecular relapse-free survival. Such patients should be considered for TKI discontinuation, particularly those who have been in deep molecular response for a long time. Stopping treatment could spare patients from treatment-induced side-effects and reduce health expenditure. Funding: ELN Foundation and France National Cancer Institute.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Richter, JohanSkåne University Hospital,Skane Univ Hosp, Dept Haematol Oncol & Radiat Phys, Lund, Sweden(Swepub:lu)med-jri
(författare)
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Guilhot, JoellePoitiers University Hospital,Ctr Hosp Univ CHU Poitiers, Ctr Invest Clin 1402, INSERM, Poitiers, France
(författare)
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Gruber, Franz X.University Hospital of North Norway,Univ Hosp North Norway, Dept Haematol, Tromso, Norway
(författare)
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Hjorth-Hansen, HenrikSt. Olav’s University Hospital,St Olavs Hosp, Dept Haematol, Trondheim, Norway
(författare)
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Almeida, AntonioInstituto Português de Oncologia do Porto Francisco Gentil (IPO),Inst Portugues Oncol Francisco Gentil, Lisbon, Portugal
(författare)
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Janssen, Jeroen J.W.M.Amsterdam UMC - Vrije Universiteit Amsterdam,Vrije Univ Amsterdam Med Ctr, Dept Haematol, Amsterdam, Netherlands,Masaryk Univ, Dept Internal Med Haematol & Oncol, Brno, Czech Republic;Univ Hosp Brno, Brno, Czech Republic,Masaryk University,University Hospital Brno
(författare)
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Mayer, JiriMasaryk University,University Hospital Brno
(författare)
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Koskenvesa, PerttuHelsinki University Central Hospital,University of Helsinki,Univ Helsinki, Haematol Res Unit Helsinki, Helsinki, Finland;Helsinki Univ Hosp, Ctr Comprehens Canc, Helsinki, Finland
(författare)
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Panayiotidis, PanayiotisNational and Kapodistrian University of Athens,Univ Athens, Dept Internal Med 1, Laikon Gen Hosp, Athens, Greece
(författare)
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Olsson-Strömberg, UllaUppsala universitet,Hematologi,Uppsala University Hospital(Swepub:uu)ulols170
(författare)
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Martinez-Lopez, Joaquin12 de Octubre University Hospital,Univ Complutense Madrid, Hosp Univ Octubre 12, Ctr Nacl Invest Oncol, Ctr Invest Biomed Red Canc, Madrid, Spain
(författare)
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Rousselot, PhilippeVersailles Saint-Quentin-en-Yvelines University,Univ Paris Saclay, Dept Haematol & Oncol, Univ Versailles St Quentin En Yvelines, Ctr Hosp Versailles,Inserm,Unite Mixte Rech 1173, Le Chesnay, France
(författare)
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Vestergaard, HanneOdense University Hospital,Odense Univ Hosp, Dept Haematol, Odense, Denmark
(författare)
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Ehrencrona, HansLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Off Med Serv, Dept Clin Genet & Pathol, Lab Med, Lund, Sweden;Lund Univ, Div Clin Genet, Lund, Sweden(Swepub:lu)med-hen
(författare)
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Kairisto, VeliTurku University Hospital,Turku Univ, Cent Hosp, Dept Clin Chem, Turku, Finland;Turku Univ, Cent Hosp, Dept Genet, Turku, Finland
(författare)
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Machová Poláková, KaterinaInstitute of Hematology and Blood Transfusion, Prauge,Inst Hematol & Blood Transfus, Prague, Czech Republic
(författare)
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Müller, Martin C.Institute for Hematology and Oncology (IHO),Inst Hematol & Oncol, Mannheim, Germany
(författare)
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Mustjoki, SatuUniversity of Helsinki,Helsinki University Central Hospital,Univ Helsinki, Haematol Res Unit Helsinki, Helsinki, Finland;Univ Helsinki, Dept Clin Chem & Haematol, Helsinki, Finland;Helsinki Univ Hosp, Ctr Comprehens Canc, Helsinki, Finland
(författare)
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Berger, Marc G.University of Auvergne,CHU Estaing, Hematol Biol & Equipe Accueil Hemopaties Chron He, Clermont Ferrand, France;Univ Clermont Auvergne, Clermont Ferrand, France
(författare)
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Fabarius, AliceHeidelberg University,Heidelberg Univ, Dept Haematol & Oncol, Univ Hosp Mannheim, Mannheim, Germany
(författare)
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Hofmann, Wolf KarstenHeidelberg University,Heidelberg Univ, Dept Haematol & Oncol, Univ Hosp Mannheim, Mannheim, Germany
(författare)
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Hochhaus, AndreasUniversitätsklinikum Jena,Univ Klinikum Jena, Klin Innere Med 2, Jena, Germany
(författare)
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Pfirrmann, MarkusLudwig-Maximilian University of Munich,Ludwig Maximilians Univ Munchen, Inst Med Informat Verarbeitung Biometrie & Epidem, Munich, Germany
(författare)
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Mahon, Francois XavierUniversity of Bordeaux,Univ Bordeaux, Bergonie Canc Inst, INSERM, Unit 916, Bordeaux, France
(författare)
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Heidelberg UniversityHeidelberg Univ, Dept Haematol & Oncol, Univ Hosp Mannheim, Mannheim, Germany
(creator_code:org_t)
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EURO-SKI investigators
Sammanhörande titlar
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Ingår i:The Lancet Oncology: Elsevier19:6, s. 747-7571470-20451474-5488
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Saussele, Susann ...
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Richter, Johan
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Guilhot, Joelle
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Gruber, Franz X.
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Hjorth-Hansen, H ...
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Almeida, Antonio
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visa fler...
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Janssen, Jeroen ...
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Mayer, Jiri
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Koskenvesa, Pert ...
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Panayiotidis, Pa ...
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Olsson-Strömberg ...
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Martinez-Lopez, ...
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Rousselot, Phili ...
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Vestergaard, Han ...
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Ehrencrona, Hans
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Kairisto, Veli
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Machová Poláková ...
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Müller, Martin C ...
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Mustjoki, Satu
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Berger, Marc G.
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Fabarius, Alice
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Hofmann, Wolf Ka ...
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Hochhaus, Andrea ...
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Pfirrmann, Marku ...
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Mahon, Francois ...
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