Clinical outcomes of second-generation tyrosine kinase inhibitors versus imatinib in older patients with CML

Cancer Sci. 2023 Mar;114(3):995-1006. doi: 10.1111/cas.15642. Epub 2022 Nov 23.

Abstract

Age and comorbidities are important factors to be considered in the selection of tyrosine kinase inhibitors (TKIs) for first-line treatment in patients with chronic myeloid leukemia in chronic phase (CML-CP). However, it is yet unclear whether TKI selection, particularly, imatinib versus second-generation TKIs (2GTKIs), impacts treatment outcomes in the clinical practice. To address this, we compared the clinical outcomes of prospectively registered 452 patients with CML-CP treated with imatinib and 2GTKIs, taking into consideration their age and/or comorbidities. A total of 136 patients (30.1%) were classified into an older cohort (≥65 years) and 316 (69.9%) into a younger cohort (18-64 years). The TKI selection did not vary based on age (70.6% received 2GTKIs in the younger cohort and 66.2% in the older cohort). The median follow-up period was 5.4 years. Treatment responses including the cumulative incidence of deep molecular response (BCR-ABL1 international scale ≤0.0032%) at any time were similar between the two age cohorts regardless of the type of TKI. The 5-year overall survival (OS) in the older cohort was lower than that in the younger cohort (95.9% vs 83.8%; p < 0.0001), whereas the 5-year OS in patients treated with 2GTKIs was not influenced by age factors and comorbidities. Therefore, our results suggest that the selection of 2GTKIs as first-line treatment is an effective option for both younger and older CML-CP patients with or without comorbidities. This trial was registered at UMIN-CTR as 00003581.

Keywords: chronic myeloid leukemia; comorbidity; imatinib; older patients; second-generation tyrosine kinase inhibitors.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Fusion Proteins, bcr-abl
  • Humans
  • Imatinib Mesylate / therapeutic use
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Protein Kinase Inhibitors / therapeutic use
  • Tyrosine Kinase Inhibitors*

Substances

  • Fusion Proteins, bcr-abl
  • Imatinib Mesylate
  • Protein Kinase Inhibitors
  • Tyrosine Kinase Inhibitors