PMID- 25703064 OWN - NLM STAT- MEDLINE DCOM- 20161013 LR - 20170930 IS - 1600-0609 (Electronic) IS - 0902-4441 (Linking) VI - 95 IP - 6 DP - 2015 Dec TI - A prospective analysis of clinical efficacy and safety in chronic myeloid leukemia-chronic phase patients with imatinib resistance or intolerance as evaluated using European LeukemiaNet 2013 criteria. PG - 558-65 LID - 10.1111/ejh.12536 [doi] AB - BACKGROUND: We conducted a phase II study to evaluate the efficacy and safety of dasatinib in Japanese patients with imatinib-resistant or imatinib-intolerant chronic myeloid leukemia (CML). METHODS: From 2009 to 2011, 54 CML-chronic phase (CP) patients with resistance (n = 40) or intolerance (n = 25) to imatinib were registered to undergo dasatinib treatment. Eleven patients showed both resistance and intolerance to imatinib. Coincidentally, the resistance criteria in this study were the same as a non-optimal response to tyrosine kinase inhibitors (TKIs) as defined in the European LeukemiaNet (ELN) 2013 recommendations. RESULTS: The overall incidence rate of major molecular response (MMR) at 12 months was 62.3% (n = 47). Forty patients with resistance to imatinib who were 'warning' and 'failure' patients based on the ELN 2013 recommendations were assessed; cumulative MMR and MR(4.5) rates were 62.5% (n = 39) and 21.0% (n = 40), respectively, at 12 months. Twelve patients who showed a BCR-ABL transcript level >1% on the international scale did not achieve a MMR or discontinued dasatinib treatment because of insufficient effects. With regard to safety issues, grade 3/4 non-hematologic adverse events (AEs) were infrequent. CONCLUSIONS: Patients with non-optimal responses (who meet ELN 2013 warning and failure criteria) to imatinib should be switched quickly to dasatinib, which is less toxic in CML-CP patients, to improve their prognoses. A BCR-ABL1 IS of <1% at 3 months of dasatinib administration is a landmark for good therapeutic outcome. CI - (c) 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Murai, Kazunori AU - Murai K AD - Department of Hematology and Oncology, Iwate Medical University, Morioka, Japan. FAU - Akagi, Tomoaki AU - Akagi T AD - Department of Hematology, Aomori Prefectural Central Hospital, Aomori, Japan. FAU - Shimosegawa, Kenji AU - Shimosegawa K AD - Department of Hematology, Iwate Prefectural Chubu Hospital, Kitakami, Japan. FAU - Sugawara, Tomohiro AU - Sugawara T AD - Department of Hematology, Osaki Citizen Hospital, Osaki, Japan. FAU - Ishizawa, Kenichi AU - Ishizawa K AD - Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan. FAU - Ito, Shigeki AU - Ito S AD - Department of Hematology and Oncology, Iwate Medical University, Morioka, Japan. FAU - Murai, Keiko AU - Murai K AD - Department of Hematology, Morioka Red Cross Hospital, Morioka, Japan. FAU - Motegi, Mutsuhito AU - Motegi M AD - Department of Internal Medicine, Omagari Kosei Medical Center, Omagari, Japan. FAU - Yokoyama, Hisayuki AU - Yokoyama H AD - Department of Hematology, National Hospital Organization, Sendai Medical Center, Sendai, Japan. FAU - Noji, Hideyoshi AU - Noji H AD - Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan. FAU - Tajima, Katsushi AU - Tajima K AD - Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology (DNHMED), Yamagata University Faculty of Medicine, Yamagata, Japan. FAU - Kimura, Jun AU - Kimura J AD - Department of Hematology, Yamagata City Hospital Saiseikan, Yamagata, Japan. FAU - Chou, Takaaki AU - Chou T AD - Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan. FAU - Ogawa, Kazuei AU - Ogawa K AD - Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan. FAU - Harigae, Hideo AU - Harigae H AD - Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan. FAU - Kubo, Kohmei AU - Kubo K AD - Department of Hematology, Aomori Prefectural Central Hospital, Aomori, Japan. FAU - Oba, Koji AU - Oba K AD - Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. AD - Interfaculty Initiative in Information Studies, The University of Tokyo, Tokyo, Japan. FAU - Sakamoto, Junichi AU - Sakamoto J AD - Tokai Central Hospital, Kakamigahara, Japan. FAU - Ishida, Yoji AU - Ishida Y AD - Department of Hematology and Oncology, Iwate Medical University, Morioka, Japan. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20150325 PL - England TA - Eur J Haematol JT - European journal of haematology JID - 8703985 RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) RN - 8A1O1M485B (Imatinib Mesylate) RN - EC 2.7.10.2 (Fusion Proteins, bcr-abl) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use MH - *Drug Resistance, Neoplasm MH - Female MH - Fusion Proteins, bcr-abl/genetics MH - Humans MH - Imatinib Mesylate/administration & dosage/adverse effects/*therapeutic use MH - Kaplan-Meier Estimate MH - Leukemia, Myeloid, Chronic-Phase/diagnosis/*drug therapy/genetics/mortality MH - Male MH - Middle Aged MH - Mutation MH - Protein Kinase Inhibitors/administration & dosage/adverse effects/*therapeutic use MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - European LeukemiaNet 2013 recommendations OT - chronic myeloid leukemia OT - dasatinib OT - major molecular response OT - molecular response >==4.5 log reduction EDAT- 2015/02/24 06:00 MHDA- 2016/10/14 06:00 CRDT- 2015/02/24 06:00 PHST- 2015/01/13 00:00 [accepted] PHST- 2015/02/24 06:00 [entrez] PHST- 2015/02/24 06:00 [pubmed] PHST- 2016/10/14 06:00 [medline] AID - 10.1111/ejh.12536 [doi] PST - ppublish SO - Eur J Haematol. 2015 Dec;95(6):558-65. doi: 10.1111/ejh.12536. Epub 2015 Mar 25.