PMID- 31462241 OWN - NLM STAT- MEDLINE DCOM- 20200120 LR - 20220114 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 19 IP - 1 DP - 2019 Aug 28 TI - Comparative efficacy and tolerability of front-line treatments for newly diagnosed chronic-phase chronic myeloid leukemia: an update network meta-analysis. PG - 849 LID - 10.1186/s12885-019-6039-9 [doi] LID - 849 AB - BACKGROUND: Recent years have witnessed the rapid evolution of therapies in chronic-phase chronic myeloid leukemia (CP-CML). To assess the efficacy and tolerability of all reported front-line treatments for patients with newly diagnosed CML, a multiple-treatments meta-analysis was performed, which accounted for both direct and indirect comparisons among those treatments. METHODS: Primary outcomes were the percentage of patients achieving major molecular response (MMR) and complete cytogenetic response (CCyR) within 12 months. Secondary outcomes included the percentage of progression to accelerated phase (AP), serious adverse effects (AEs), overall discontinuation and discontinuation for drug-related AEs. Direct pairwise meta-analysis and indirect multi-comparison meta-analysis among those treatments in each outcome were both conducted. The surface under the cumulative ranking curve (SUCRA) was calculated for all treatments in each outcome. Cluster analysis demonstrated the division of treatments into distinct groupings according to efficacy and tolerability profiles. RESULTS: A total of 21 randomized controlled trials (RCTs, including 10,187 patients) comparing 15 different interventions for CP-CML patients were included in this study. SUCRA analysis suggested that all tyrosine kinase inhibitors (TKIs) are highly effective in newly diagnosed CP-CML when compared to traditional drugs. Newer TKIs and higher-dose imatinib generally resulted in faster cytogenetic and molecular responses when compared with standard-dose imatinib and traditional drugs. Furthermore, traditional drugs, higher-dose imatinib and newer TKIs demonstrated lower acceptability than standard-dose imatinib. One cluster of interventions, which included nilotinib (300/400 mg BID), dasatinib (100 mg QD) and radotinib (300 mg BID), demonstrated higher efficacy and tolerability than other treatments. CONCLUSIONS: Nilotinib (300/400 mg BID), dasatinib (100 mg QD) and radotinib (300 mg BID) prove to be the most recommended front-line treatments of the greatest efficacy and tolerability for CP-CML patients. High-dose therapies are recommended only for patients in accelerated phase/blast phase or with suboptimal CML-CP response, and management of adverse events should be carried out to avoid compromising the clinical efficacy. FAU - Tang, Lu AU - Tang L AD - Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022,, Hubei, China. AD - Hubei clinical medical center of cell therapy for neoplastic disease, Wuhan, Hubei, China. FAU - Zhang, Huan AU - Zhang H AD - Instisute of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1227 Jiefang road, Wuhan, 430022,, Hubei, China. FAU - Peng, Yi-Zhong AU - Peng YZ AD - Instisute of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1227 Jiefang road, Wuhan, 430022,, Hubei, China. FAU - Li, Cheng-Gong AU - Li CG AD - Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022,, Hubei, China. AD - Hubei clinical medical center of cell therapy for neoplastic disease, Wuhan, Hubei, China. FAU - Jiang, Hui-Wen AU - Jiang HW AD - Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022,, Hubei, China. AD - Hubei clinical medical center of cell therapy for neoplastic disease, Wuhan, Hubei, China. FAU - Xu, Min AU - Xu M AD - Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022,, Hubei, China. FAU - Mei, Heng AU - Mei H AUID- ORCID: 0000-0001-7941-2443 AD - Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022,, Hubei, China. hmei@hust.edu.cn. AD - Hubei clinical medical center of cell therapy for neoplastic disease, Wuhan, Hubei, China. hmei@hust.edu.cn. AD - Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, Hubei, China. hmei@hust.edu.cn. FAU - Hu, Yu AU - Hu Y AD - Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022,, Hubei, China. dr_huyu@126.com. AD - Hubei clinical medical center of cell therapy for neoplastic disease, Wuhan, Hubei, China. dr_huyu@126.com. AD - Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, Hubei, China. dr_huyu@126.com. LA - eng GR - No. 81770132/National Natural Science Foundation of China/ GR - No. 81570116/National Natural Science Foundation of China/ GR - No. 2018ACA141/the Science and Technology Department of Hubei Province/ PT - Comparative Study PT - Journal Article DEP - 20190828 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (4-methyl-N-(3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl)-3-(4-pyrazin-2-ylpyrimidin-2-ylamino)benzamide) RN - 0 (Benzamides) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrazines) RN - 0 (Pyrimidines) RN - 8A1O1M485B (Imatinib Mesylate) RN - F41401512X (nilotinib) RN - RBZ1571X5H (Dasatinib) SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects MH - Benzamides/administration & dosage/adverse effects MH - Dasatinib/administration & dosage/adverse effects MH - Dose-Response Relationship, Drug MH - Female MH - Humans MH - Imatinib Mesylate/administration & dosage/adverse effects MH - Leukemia, Myeloid, Chronic-Phase/*drug therapy MH - Male MH - Network Meta-Analysis MH - Protein Kinase Inhibitors/*administration & dosage/adverse effects MH - Pyrazines/administration & dosage/adverse effects MH - Pyrimidines/administration & dosage/adverse effects MH - Survival Analysis MH - Treatment Outcome PMC - PMC6714291 OTO - NOTNLM OT - Chronic myeloid leukemia OT - Efficacy OT - Network meta-analysis OT - Tolerability OT - Tyrosine kinase inhibitors COIS- The authors declare that they have no competing interests. EDAT- 2019/08/30 06:00 MHDA- 2020/01/21 06:00 PMCR- 2019/08/28 CRDT- 2019/08/30 06:00 PHST- 2019/01/30 00:00 [received] PHST- 2019/08/14 00:00 [accepted] PHST- 2019/08/30 06:00 [entrez] PHST- 2019/08/30 06:00 [pubmed] PHST- 2020/01/21 06:00 [medline] PHST- 2019/08/28 00:00 [pmc-release] AID - 10.1186/s12885-019-6039-9 [pii] AID - 6039 [pii] AID - 10.1186/s12885-019-6039-9 [doi] PST - epublish SO - BMC Cancer. 2019 Aug 28;19(1):849. doi: 10.1186/s12885-019-6039-9.