Comparative efficacy and safety of different doses of ponatinib versus other tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia: a systematic review and network meta-analysis

Expert Opin Drug Saf. 2024 Jan;23(1):37-45. doi: 10.1080/14740338.2023.2273339. Epub 2023 Oct 26.

Abstract

Objective: Ponatinib was recommended with caution because of its high risk of causing arterial occlusion events in chronic myeloid leukemia (CML) patients. The purpose of this study was to understand the efficacy and safety of different doses of ponatinib in the treatment of CML, and to compare it with other tyrosine kinase inhibitors (TKIs).

Method: A network meta-analysis (NMA) was conducted by searching randomized controlled trials (RCTs) of ponatinib in patients with CML to compare the efficacy and safety of ponatinib, and ranked under the cumulative ranking curve (SUCRA) to evaluate the optimal treatment.

Results: A total of seven articles with eight RCTs were included in this study, involving 45 mg, 30 mg and 15 mg ponatinib doses. Seven outcome indexes were analyzed. The results showed that 45 mg ponatinib was superior to other doses of ponatinib and other TKIs in CCyR, MCyR and CHR, but the incidence of SAEs and AOEs was significantly higher than other treatment regimens.

Conclusion: Ponatinib, with an initial dosage of 45 mg and a gradual reduction to 15 mg, may be a more favorable option for patients with CML at all stages of disease progression, rather than just those in the chronic phase of CML.

Keywords: CML; Ponatinib; efficacy; network meta-analysis; safety.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Chronic Disease
  • Humans
  • Imidazoles*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Network Meta-Analysis
  • Protein Kinase Inhibitors
  • Pyridazines* / adverse effects
  • Tyrosine Kinase Inhibitors

Substances

  • ponatinib
  • Tyrosine Kinase Inhibitors
  • Pyridazines
  • Protein Kinase Inhibitors
  • Antineoplastic Agents
  • Imidazoles