Systematic Review and Meta-Analysis of -New-Generation Tyrosine Kinase Inhibitors versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia

Acta Haematol. 2020;143(3):204-216. doi: 10.1159/000501537. Epub 2019 Sep 12.

Abstract

Backgrounds: We performed this systematic review and meta-analysis to compare the efficacy of new-generation tyrosine kinase inhibitors (NG-TKIs; including dasatinib, nilotinib, bosutinib, radotinib, and ponatinib) versus imatinib for patients with newly diagnosed chronic myeloid leukemia (CML).

Summary: We identified randomized controlled trials comparing the efficacy of NG-TKIs versus imatinib as the first-line treatment for CML patients by searching the PubMed, Cochrane library, and EMBASE databases. Two reviewers independently extracted data and assessed study quality. A meta-analysis was performed to calculate risk ratios and 95% CIs using a fixed-effects model.Our study included 10 trials. Overall, treatment with NG-TKIs significantly improved the major molecular response and MR4.5 at all time points, and early molecular response at 3 months. Importantly, overall survival (OS) was significantly higher with the NG-TKIs at 12 months. Besides, NG-TKI-treated patients showed a significantly lower CML-related death and progression to the accelerated phase/blast crisis. Key Messages: In first-line treatment, NG-TKIs are superior to imatinib regarding OS at 12 months, and because molecular response rates were higher with the NG-TKIs at all time points, the NG-TKIs favor treatment-free remission.

Keywords: Chronic myeloid leukemia; Imatinib; Meta-analysis; Tyrosine kinase inhibitor.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Hematologic Diseases / chemically induced
  • Humans
  • Imatinib Mesylate / adverse effects
  • Imatinib Mesylate / therapeutic use*
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / genetics
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Survival Analysis
  • Young Adult

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Imatinib Mesylate