TY - JOUR
T1 - Comparative Effectiveness of Newer Tyrosine Kinase Inhibitors Versus Imatinib in the First-Line Treatment of Chronic-Phase Chronic Myeloid Leukemia Across Risk Groups
T2 - A Systematic Review and Meta-Analysis of Eight Randomized Trials
AU - Yun, Seongseok
AU - Vincelette, Nicole D.
AU - Segar, Jennifer M.
AU - Dong, Yimin
AU - Shen, Yang
AU - Kim, Dong Wook
AU - Abraham, Ivo
N1 - Funding Information:
We gratefully acknowledge the comments and suggestions from B. D. Smith (Johns Hopkins). This work was supported by predoctoral fellowships to N.D.V. from the Mayo Foundation for Education and Research and a Bressler Alpert Society Research Grant to S.Y. from the University of Arizona.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Background 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). Materials and Methods 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. Results 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. Conclusion 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.
AB - Background 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). Materials and Methods 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. Results 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. Conclusion 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.
KW - Bosutinib
KW - Dasatinib
KW - Nilotinib
KW - Ponatinib
KW - Radotinib
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U2 - 10.1016/j.clml.2016.03.003
DO - 10.1016/j.clml.2016.03.003
M3 - Article
C2 - 27101984
AN - SCOPUS:84974575344
VL - 16
SP - e85-e94
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
SN - 2152-2669
IS - 6
ER -