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.
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).



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.



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.



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.
Department of Medicine, University of Arizona, Tucson, AZ; Hematology and Oncology, H. Lee Moffitt Cancer Center, Tampa, FL. Electronic address: syun@email.arizona.edu.
Seongseok
S
Yun
Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN.
Nicole D
ND
Vincelette
Department of Medicine, University of Arizona, Tucson, AZ.
Jennifer M
JM
Segar
Department of Pathology, University of Arizona, Tucson, AZ.
Yimin
Y
Dong
Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Yang
Y
Shen
Department of Hematology, Leukemia Research Institute, The Catholic University of Korea, Seoul, South Korea.
Dong-Wook
DW
Kim
Arizona Cancer Center, University of Arizona, Tucson, AZ; Center for Health Outcomes and PharmacoEconomic Research, University of Arizona, Tucson, AZ.
Ivo
I
Abraham
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage / Q000627:therapeutic use*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D009154:Mutation; D016017:Odds Ratio; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
Bosutinib; Dasatinib; Nilotinib; Ponatinib; Radotinib