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- Title
Comparative Effectiveness of Newer Tyrosine Kinase Inhibitors Versus Imatinib in the First-Line Treatment of Chronic-Phase Chronic Myeloid Leukemia Across Risk Groups: A Systematic Review and Meta-Analysis of Eight Randomized Trials.
- Authors
Yun, Seongseok; Vincelette, Nicole D.; Segar, Jennifer M.; Dong, Yimin; Shen, Yang; Kim, Dong-Wook; Abraham, Ivo
- Abstract
<bold>Background: </bold>BCR-ABL1 tyrosine kinase inhibitors (TKIs) have significantly improved the survival outcomes for patients with chronic myeloid leukemia (CML). In addition to imatinib, 3 newer generation TKIs (NG-TKIs) have been approved as first-line treatment of chronic phase (CP)-CML. These have been preferably used in patients with CP-CML with a high Sokal or Hasford risk score. We performed a systematic review and meta-analysis to compare the outcomes with NG-TKIs as a category versus imatinib in patients with newly diagnosed CP-CML and to indirectly compare the efficacy of NG-TKIs among each other. Furthermore, we assessed the effect of the risk scores on the complete cytogenetic response (CCyR) and major molecular response (MMR).<bold>Materials and Methods: </bold>The eligible studies were limited to randomized controlled trials comparing the efficacy of first-line treatment using NG-TKIs versus imatinib in adult patients (aged ≥ 18 years) with CP-CML.<bold>Results: </bold>The differences in the CCyR, progression-free survival, and overall survival between the NG-TKIs and imatinib were not statistically significant. NG-TKI-treated patients showed a significantly greater likelihood of MMR (relative risk [RR], 0.76; 95% confidence interval, 0.63-0.91; P = .003) and lower likelihood of progression to an accelerated phase/blast crisis (RR, 0.37; 95% confidence interval, 0.20-0.67; P = .001) than did imatinib-treated patients. Nilotinib, dasatinib, and radotinib showed significantly greater CCyR rates compared with bosutinib and ponatinib. All risk groups showed statistically equivalent benefits from NG-TKIs for the CCyR and MMR.<bold>Conclusion: </bold>In first-line treatment, the NG-TKIs as a category showed greater effectiveness in MMR and prevention of accelerated phase/blast crisis progression. Risk stratification was not found to affect the RR of CCyR and MMR.
- Subjects
ANTINEOPLASTIC agents; CLINICAL trials; COMPARATIVE studies; RESEARCH methodology; MEDICAL cooperation; META-analysis; GENETIC mutation; PROTEINS; RESEARCH; SYSTEMATIC reviews; EVALUATION research; CHRONIC myeloid leukemia; TREATMENT effectiveness; DISEASE progression; PUBLICATION bias; PROTEIN kinase inhibitors; ODDS ratio; DIAGNOSIS; THERAPEUTICS
- Publication
Clinical Lymphoma, Myeloma & Leukemia, 2016, Vol 16, Issue 6, pe85
- ISSN
2152-2650
- Publication type
journal article
- DOI
10.1016/j.clml.2016.03.003