{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:32:27Z","timestamp":1791307947749,"version":"4.3.1"},"reference-count":79,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T00:00:00Z","timestamp":1450828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>The advent of tyrosine kinase inhibitors (TKIs) has drastically changed the treatment outcome of chronic myeloid leukemia (CML). Imatinib was the first TKI approved, and has been considered the standard of care for more than a decade. Second generation compounds, namely dasatinib and nilotinib, are highly effective in newly diagnosed patients as well as those who fail imatinib. Second generation TKIs have been demonstrated to induce deeper and faster responses compared to imatinib, however no survival advantage has been observed so far. Today, the expected survival of CML patients, if properly managed, is likely to be similar to the general population. Clinicians are faced the challenge of making decision for which TKI to choose upfront. Comorbidities of the patient, the side effect profile, and the cost of the TKI of interest should be an important consideration in decision making. Whatever TKI is chosen as frontline, noncompliance or treatment failure should be recognized early as a prompt intervention increases the chance of achieving best possible response. Herein, we review the frontline options for the management of patients with CML and how to best choose these agents. Am. J. Hematol. 91:59\u201366, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.24249","type":"journal-article","created":{"date-parts":[[2015,11,24]],"date-time":"2015-11-24T09:33:05Z","timestamp":1448357585000},"page":"59-66","source":"Crossref","is-referenced-by-count":57,"title":["Chronic myeloid leukemia: First\u2010line drug of choice"],"prefix":"10.1002","volume":"91","author":[{"given":"Elias","family":"Jabbour","sequence":"first","affiliation":[{"name":"Department of Leukemia The University of Texas M. D. Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,23]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"751","article-title":"The molecular biology of chronic myeloid leukaemia","volume":"10","author":"Melo JV.","year":"1996","journal-title":"Leukemia"},{"key":"e_1_2_7_3_1","first-page":"247","article-title":"Constitutive activation of STAT5 by the BCR\u2013ABL oncogene in chronic myelogenous leukemia","volume":"13","author":"Shuai K","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.25.11746"},{"key":"e_1_2_7_5_1","volume-title":"and Figures 2015","author":"American Cancer Society.","year":"2015"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.26679"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.2.398.398"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-122-4-199502150-00003"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199707243370402"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0596-561"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011573"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022457"},{"key":"e_1_2_7_13_1","first-page":"1126","article-title":"International randomized study of interferon vs STI571 (IRIS) 8\u2010year follow up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with imatinib","volume":"114","author":"Deininger M","year":"2009","journal-title":"ASH Annual Meeting Abstracts"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.3869"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.3724"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-014-1566-2"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.32.0598"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-12-191254"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1004095"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25438"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe068073"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055229"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.9260"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-10-532341"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1002315"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-06-511592"},{"key":"e_1_2_7_27_1","first-page":"152","article-title":"Final study results of the phase 3 dasatinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase (CML\u2010CP) trial (DASISION, CA180\u2010056)","volume":"124","author":"Cortes J","year":"2014","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_7_28_1","first-page":"517","article-title":"Spirit 2: An NCRI randomized study comparing dasatinib with imatinib in patients with newly diagnosed CML","volume":"124","author":"O'Brien SG","year":"2014","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603170"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055104"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-03-080689"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912614"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.134"},{"key":"e_1_2_7_34_1","doi-asserted-by":"crossref","first-page":"7073","DOI":"10.1200\/jco.2014.32.15_suppl.7073","article-title":"ENESTnd 5\u2010year (y) update: Long\u2010term outcomes of patients (pts) with chronic myeloid leukemia in chronic phase (CML\u2010CP) treated with frontline nilotinib (NIL) versus imatinib (IM)","volume":"32","author":"Larson RA","year":"2014","journal-title":"J Clin Oncol (Meeting Abstracts)"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1199"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-355594"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.7522"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.09.028"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306494"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(15)00127-1"},{"key":"e_1_2_7_41_1","article-title":"Epic: A phase 3 trial of ponatinib compared with imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML\u2010CP)","author":"Lipton JH.","journal-title":"ASH 2014 Abstract 519."},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.0329"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24734"},{"key":"e_1_2_7_44_1","unstructured":"Sprycel (dasatinib) Package Insert.Princeton NJ. Bristol\u2010Myers Squibb Company. 5\/2014."},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-180604"},{"key":"e_1_2_7_46_1","unstructured":"Tasigna (nilotinib) Package Insert.East Hanover NJ. Novartis Pharmaceuticals Corporation. 1\/2014."},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.22037"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2012.04.005"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.22051"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.69"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V63.4.789.789"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/90.11.850"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-093617"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.26.5819"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.056457"},{"key":"e_1_2_7_56_1","first-page":"814","article-title":"KIR2DL5B genotype independently predicts poor outcomes in CML\u2010CP patients switched to nilotinib after suboptimal responses to imatinib and may refine prognosis in patients with EMR failure","volume":"124","author":"Yeung DT","year":"2014","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.180"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21262"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.49.1845"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsb1013826"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-03-490003"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djr060"},{"key":"e_1_2_7_63_1","unstructured":"Gleevec (imatinib) Package Insert.East Hanover NJ. Novartis Pharmaceuticals Corporation. 10\/2013."},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.4103\/0971-5851.123716"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.0779"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-05-501569"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-229864"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.33.9176"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.18.6999"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.6565"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-03-490128"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-11-466037"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.090282"},{"key":"e_1_2_7_74_1","first-page":"254","article-title":"Any BRC\u2010ABL reduction below 10% at 6 months of therapy significantly improves outcome for CML patients with a poor response at 3 months","volume":"122","author":"Branford S","year":"2013","journal-title":"Blood"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.36.0693"},{"key":"e_1_2_7_76_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1182\/blood.V122.21.95.95","article-title":"Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with suboptimal cytogenetic response on imatinib: First results of the LASOR trial","volume":"122","author":"Cortes JE","year":"2013","journal-title":"Blood"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70233-3"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-02-483750"},{"key":"e_1_2_7_79_1","first-page":"151","article-title":"Interim analysis of a pan european stop tyrosine kinase inhibitor trial in chronic myeloid leukemia: The EURO\u2010SKI Study","volume":"124","author":"Mahon F","year":"2014","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"e_1_2_7_80_1","first-page":"811","article-title":"Dasatinib or nilotinib discontinuation in chronic phase (CP)\u2010chronic myeloid leukemia (CML) patients (pts) with durably undetectable BCR\u2013ABL transcripts: Interim analysis of the STOP 2G\u2010TKI study with a minimum follow\u2010up of 12 Months\u2014on Behalf of the French CML Group Filmc","volume":"124","author":"Rea D","year":"2014","journal-title":"Blood (ASH Annual Meeting Abstracts)"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.24249","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.24249","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:09:05Z","timestamp":1694477345000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.24249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,23]]},"references-count":79,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1002\/ajh.24249"],"URL":"https:\/\/doi.org\/10.1002\/ajh.24249","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,23]]}}}