{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T07:22:35Z","timestamp":1770967355420,"version":"3.50.1"},"reference-count":49,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,12,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>With the approval in many countries of nilotinib and dasatinib for frontline therapy in chronic myeloid leukemia, clinicians now have to make a difficult choice. Because none of the 3 available tyrosine kinase inhibitors (TKIs) have shown a clear survival advantage, they all represent reasonable choices. However, in individual patients, the case may be stronger for a particular TKI. In the younger patient, in whom the prospect of eventually achieving treatment-free remission is likely to be of great importance, dasatinib or nilotinib may be preferred, although their advantage over imatinib in this setting remains to be proven. In patients with a higher risk of transformation (which is currently based on prognostic scoring), the more potent TKIs may be preferred because they appear to be more effective at reducing the risk of transformation to BC. However, imatinib still represents an excellent choice for many chronic myeloid leukemia patients. All of these considerations need to be made in the context of the patient's comorbidities, which may lead to one or more TKIs being ruled out of contention. Whatever first choice of TKI is made, treatment failure or intolerance must be recognized early because a prompt switch to another TKI likely provides the best chance of achieving optimal response.<\/jats:p>","DOI":"10.1182\/asheducation-2013.1.168","type":"journal-article","created":{"date-parts":[[2013,12,6]],"date-time":"2013-12-06T10:51:13Z","timestamp":1386327073000},"page":"168-175","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":40,"title":["Which TKI? An embarrassment of riches for chronic myeloid leukemia patients"],"prefix":"10.1182","volume":"2013","author":[{"given":"Timothy","family":"Hughes","sequence":"first","affiliation":[{"name":"South Australian Health and Medical Research Institute, SA Pathology, and University of Adelaide, Adelaide, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"White","sequence":"additional","affiliation":[{"name":"South Australian Health and Medical Research Institute, SA Pathology, and University of Adelaide, Adelaide, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2019111703324216200_B1","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1038\/leu.2009.38","article-title":"Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia","volume":"23","author":"Hochhaus","year":"2009","journal-title":"Leukemia"},{"key":"2019111703324216200_B2","doi-asserted-by":"crossref","first-page":"4445","DOI":"10.1200\/JCO.2006.09.9499","article-title":"Measurement of in vivo BCR-ABL kinase inhibition to monitor imatinib-induced target blockade and predict response in chronic myeloid leukemia","volume":"25","author":"White","year":"2007","journal-title":"J Clin Oncol"},{"key":"2019111703324216200_B3","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1182\/blood-2005-03-1103","article-title":"In vitro sensitivity to imatinib-induced inhibition of ABL kinase activity is predictive of molecular response in patients with de novo CML","volume":"106","author":"White","year":"2005","journal-title":"Blood"},{"key":"2019111703324216200_B4","doi-asserted-by":"crossref","first-page":"4022","DOI":"10.1182\/blood-2007-10-116475","article-title":"Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study","volume":"111","author":"Larson","year":"2008","journal-title":"Blood"},{"key":"2019111703324216200_B5","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1182\/blood-2006-07-036012","article-title":"Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia","volume":"109","author":"Picard","year":"2007","journal-title":"Blood"},{"key":"2019111703324216200_B6","doi-asserted-by":"crossref","first-page":"3739","DOI":"10.1182\/blood-2003-12-4276","article-title":"Active transport of imatinib into and out of cells: implications for drug resistance","volume":"104","author":"Thomas","year":"2004","journal-title":"Blood"},{"key":"2019111703324216200_B7","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1182\/blood-2005-11-4687","article-title":"OCT-1-mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib","volume":"108","author":"White","year":"2006","journal-title":"Blood"},{"key":"2019111703324216200_B8","doi-asserted-by":"crossref","first-page":"907","DOI":"10.3324\/haematol.2011.056457","article-title":"Chronic phase chronic myeloid leukemia patients with low OCT-1 activity randomized to high-dose imatinib achieve better responses and have lower failure rates than those randomized to standard-dose imatinib","volume":"97","author":"White","year":"2012","journal-title":"Haematologica"},{"key":"2019111703324216200_B9","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1182\/blood-2007-06-093617","article-title":"Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: higher doses of imatinib may overcome the negative impact of low OCT-1 activity","volume":"110","author":"White","year":"2007","journal-title":"Blood"},{"key":"2019111703324216200_B10","doi-asserted-by":"crossref","first-page":"5426","DOI":"10.1182\/blood-2009-08-215939","article-title":"Selecting optimal second-line tyrosine kinase inhibitor therapy for chronic myeloid leukemia patients after imatinib failure: does the BCR-ABL mutation status really matter?","volume":"114","author":"Branford","year":"2009","journal-title":"Blood"},{"issue":"18","key":"2019111703324216200_B11","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1182\/blood-2012-04-423418","article-title":"Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase","volume":"121","author":"Hochhaus","year":"2013","journal-title":"Blood"},{"key":"2019111703324216200_B12","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1056\/NEJMoa0912614","article-title":"Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia","volume":"362","author":"Saglio","year":"2010","journal-title":"N Engl J Med"},{"key":"2019111703324216200_B13","doi-asserted-by":"crossref","first-page":"4204","DOI":"10.1200\/JCO.2009.21.8230","article-title":"Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase","volume":"27","author":"Hughes","year":"2009","journal-title":"J Clin Oncol"},{"key":"2019111703324216200_B14","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S1470-2045(11)70201-7","article-title":"Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial","volume":"12","author":"Kantarjian","year":"2011","journal-title":"Lancet Oncol"},{"key":"2019111703324216200_B15","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1002\/ajh.22037","article-title":"Progressive peripheral arterial occlusive disease and other vascular events during nilotinib therapy in CML","volume":"86","author":"Aichberger","year":"2011","journal-title":"Am J Hematol"},{"issue":"6","key":"2019111703324216200_B16","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1038\/leu.2013.70","article-title":"Peripheral artery occlusive disease in chronic phase chronic myeloid leukemia patients treated with nilotinib or imatinib","volume":"27","author":"Kim","year":"2013","journal-title":"Leukemia"},{"key":"2019111703324216200_B17","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.leukres.2013.01.006","article-title":"Considerations for early switch to nilotinib or dasatinib in patients with chronic myeloid leukemia with inadequate response to first-line imatinib","volume":"37","author":"Quint\u00e1s-Cardama","year":"2013","journal-title":"Leuk Res"},{"issue":"6","key":"2019111703324216200_B18","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/leu.2013.69","article-title":"Rates of peripheral arterial occlusive disease in patients with chronic myeloid leukemia in the chronic phase treated with imatinib, nilotinib, or non-tyrosine kinase therapy: a retrospective cohort analysis","volume":"27","author":"Giles","year":"2013","journal-title":"Leukemia"},{"issue":"21","key":"2019111703324216200_B19","first-page":"1686","article-title":"Incidence of hyperglycemia by 3 years in patients (Pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with nilotinib (NIL) or imatinib (IM) in \u0395\u039d\u0395S\u03a4nd [abstract]","volume":"120","author":"Rea","year":"2012","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"2019111703324216200_B20","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1182\/blood-2011-08-376087","article-title":"Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION)","volume":"119","author":"Kantarjian","year":"2012","journal-title":"Blood"},{"key":"2019111703324216200_B21","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1161\/CIRCULATIONAHA.111.079921","article-title":"Pulmonary arterial hypertension in patients treated by dasatinib","volume":"125","author":"Montani","year":"2012","journal-title":"Circulation"},{"issue":"21","key":"2019111703324216200_B22","first-page":"691","article-title":"Relative increase of lymphocytes as early as 1 month after initiation of dasatinib is a reliable predictor for achieving complete molecular response at 12 months in chronic phase CML patients treated with dasatinib [abstract]","volume":"120","author":"Matsuki","year":"2012","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"2019111703324216200_B23","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/S1470-2045(10)70233-3","article-title":"Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial","volume":"11","author":"Mahon","year":"2010","journal-title":"Lancet Oncol"},{"key":"2019111703324216200_B24","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1038\/leu.2010.185","article-title":"Patients with chronic myeloid leukemia who maintain a complete molecular response after stopping imatinib treatment have evidence of persistent leukemia by DNA PCR","volume":"24","author":"Ross","year":"2010","journal-title":"Leukemia"},{"issue":"4","key":"2019111703324216200_B25","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1182\/blood-2013-02-483750","article-title":"Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study","volume":"122","author":"Ross","year":"2013","journal-title":"Blood"},{"issue":"19","key":"2019111703324216200_B26","doi-asserted-by":"crossref","first-page":"3818","DOI":"10.1182\/blood-2012-10-462291","article-title":"Early molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML","volume":"121","author":"Branford","year":"2013","journal-title":"Blood"},{"issue":"21","key":"2019111703324216200_B27","first-page":"961","article-title":"Discontinuation of second generation (2G) tyrosine kinase inhibitors (TKI) in chronic phase (CP)-chronic myeloid leukemia (CML) patients with stable undetectable BCR-ABL transcripts [abstract]","volume":"120","author":"Rea","year":"2012","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"2019111703324216200_B28","doi-asserted-by":"crossref","first-page":"3898","DOI":"10.1182\/blood-2012-02-410688","article-title":"A randomized trial of dasatinib 100 mg versus imatinib 400 mg in newly diagnosed chronic-phase chronic myeloid leukemia","volume":"120","author":"Radich","year":"2012","journal-title":"Blood"},{"key":"2019111703324216200_B29","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1182\/blood-2010-03-273979","article-title":"Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS)","volume":"116","author":"Hughes","year":"2010","journal-title":"Blood"},{"issue":"21","key":"2019111703324216200_B30","first-page":"3771","article-title":"Early switch to nilotinib does not overcome the adverse outcome for CML patients failing to achieve early molecular response on imatinib, despite excellent overall outcomes in the TIDEL II trial [abstract]","volume":"120","author":"Yeung","year":"2012","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"2019111703324216200_B31","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1038\/leu.2010.188","article-title":"OCT-1 activity measurement provides a superior imatinib response predictor than screening for single-nucleotide polymorphisms of OCT-1","volume":"24","author":"White","year":"2010","journal-title":"Leukemia"},{"issue":"21","key":"2019111703324216200_B32","first-page":"693","article-title":"Early molecular response to imatinib in CP-CML patients: the significance of early dose intensity and OCT-1 activity in responders and efficacy of dose escalation and switch to nilotinib in non-responders [abstract]","volume":"120","author":"White","year":"2012","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"2019111703324216200_B33","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1200\/JCO.2009.26.5819","article-title":"Functional activity of the OCT-1 protein is predictive of long-term outcome in patients with chronic-phase chronic myeloid leukemia treated with imatinib","volume":"28","author":"White","year":"2010","journal-title":"J Clin Oncol"},{"key":"2019111703324216200_B34","doi-asserted-by":"crossref","first-page":"6660","DOI":"10.1182\/blood-2010-08-304477","article-title":"Cancerous inhibitor of PP2A (CIP2A) at diagnosis of chronic myeloid leukemia is a critical determinant of disease progression","volume":"117","author":"Lucas","year":"2011","journal-title":"Blood"},{"key":"2019111703324216200_B35","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1038\/leu.2012.19","article-title":"Gfi-1 inhibits proliferation and colony formation of p210BCR\/ABL-expressing cells via transcriptional repression of STAT 5 and Mcl-1","volume":"26","author":"Soliera","year":"2012","journal-title":"Leukemia"},{"key":"2019111703324216200_B36","doi-asserted-by":"crossref","first-page":"7949","DOI":"10.1158\/0008-5472.CAN-10-1667","article-title":"Expression of the transcriptional repressor Gfi-1 is regulated by C\/EBP{alpha} and is involved in its proliferation and colony formation-inhibitory effects in p210BCR\/ABL-expressing cells","volume":"70","author":"Lidonnici","year":"2010","journal-title":"Cancer Res"},{"issue":"6","key":"2019111703324216200_B37","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1038\/leu.2013.47","article-title":"Low GFI1 expression in white blood cells of CP-CML patients at diagnosis is strongly associated with subsequent blastic transformation","volume":"27","author":"Kok","year":"2013","journal-title":"Leukemia"},{"key":"2019111703324216200_B38","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1073\/pnas.0510423103","article-title":"Gene expression changes associated with progression and response in chronic myeloid leukemia","volume":"103","author":"Radich","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2019111703324216200_B39","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1182\/blood-2009-03-210732","article-title":"A gene expression signature of CD34+ cells to predict major cytogenetic response in chronic-phase chronic myeloid leukemia patients treated with imatinib","volume":"115","author":"McWeeney","year":"2010","journal-title":"Blood"},{"key":"2019111703324216200_B40","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/nm.2713","article-title":"A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer","volume":"18","author":"Ng","year":"2012","journal-title":"Nat Med"},{"key":"2019111703324216200_B41","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1038\/bjc.2012.173","article-title":"Contrasting effects of diclofenac and ibuprofen on active imatinib uptake into leukaemic cells","volume":"106","author":"Wang","year":"2012","journal-title":"Br J Cancer"},{"key":"2019111703324216200_B42","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3324\/haematol.2009.012781","article-title":"Early prediction of success or failure of treatment with second-generation tyrosine kinase inhibitors in patients with chronic myeloid leukemia","volume":"95","author":"Milojkovic","year":"2010","journal-title":"Haematologica"},{"key":"2019111703324216200_B43","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/leu.2012.305","article-title":"Prediction of outcomes in patients with Ph+ chronic myeloid leukemia in chronic phase treated with nilotinib after imatinib resistance\/intolerance","volume":"27","author":"Jabbour","year":"2013","journal-title":"Leukemia"},{"key":"2019111703324216200_B44","doi-asserted-by":"crossref","first-page":"4323","DOI":"10.1200\/JCO.2011.40.5217","article-title":"Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib","volume":"30","author":"Branford","year":"2012","journal-title":"J Clin Oncol"},{"issue":"21","key":"2019111703324216200_B45","first-page":"163","article-title":"A pivotal phase 2 trial of ponatinib in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) resistant or intolerant to dasatinib or nilotinib, or with the T315I BCR-ABL mutation: 12-month follow-up of the PACE trial [abstract]","volume":"120","author":"Cortes","year":"2012","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"2019111703324216200_B46","doi-asserted-by":"crossref","first-page":"3486","DOI":"10.1200\/JCO.2011.38.7522","article-title":"Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial","volume":"30","author":"Cortes","year":"2012","journal-title":"J Clin Oncol"},{"key":"2019111703324216200_B47","doi-asserted-by":"crossref","first-page":"4567","DOI":"10.1182\/blood-2011-05-355594","article-title":"Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib","volume":"118","author":"Cortes","year":"2011","journal-title":"Blood"},{"issue":"21","key":"2019111703324216200_B48","first-page":"3747","article-title":"Multivariate analyses of the clinical and molecular parameters associated with efficacy and safety in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) treated with ponatinib in the PACE trial [abstract]","volume":"120","author":"Mauro","year":"2012","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"2019111703324216200_B49","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1056\/NEJMoa1004095","article-title":"Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia","volume":"363","author":"Preudhomme","year":"2010","journal-title":"N Engl J Med"}],"container-title":["Hematology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2013\/1\/168\/1249313\/bep00113000168.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2013\/1\/168\/1249313\/bep00113000168.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,17]],"date-time":"2019-11-17T03:32:57Z","timestamp":1573961577000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/hematology\/article\/2013\/1\/168\/20711\/Which-TKI-An-embarrassment-of-riches-for-chronic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,6]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12,6]]}},"URL":"https:\/\/doi.org\/10.1182\/asheducation-2013.1.168","relation":{},"ISSN":["1520-4391","1520-4383"],"issn-type":[{"value":"1520-4391","type":"print"},{"value":"1520-4383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,6]]}}}