Asciminib in Patients With CML-CP Previously Treated With ≥ 2 Tyrosine Kinase Inhibitors: 96-Week Results From the Japanese Subgroup Analysis of the ASCEMBL Study

Int J Hematol. 2024 Sep;120(3):305-313. doi: 10.1007/s12185-024-03805-0. Epub 2024 Jun 18.

Abstract

Asciminib is a first-in-class BCR::ABL1 inhibitor that Specifically Targets the ABL1 Myristoyl Pocket (STAMP). It is approved worldwide and in Japan for chronic myeloid leukemia in chronic phase (CML-CP) with resistance or intolerance to previous tyrosine kinase inhibitor (TKI) therapy. In the Phase 3 ASCEMBL study, patients with CML-CP who received ≥ 2 prior ATP-competitive TKIs were randomized (2:1) to asciminib 40 mg twice-daily or bosutinib 500 mg once-daily. Here, we report the 96-week results of the subgroup analysis of Japanese patients (asciminib, n = 13; bosutinib, n = 3) in the ASCEMBL study. The MMR rate at Week 96 was 46.2% in asciminib-treated patients, increasing from Weeks 24 and 48. Patients who achieved MMR at Week 24 remained in MMR up to the Week 96 cutoff. While a high proportion of patients treated with asciminib remained on treatment at cutoff, none randomized to bosutinib were on treatment at Week 96. Despite the longer duration of exposure to asciminib, its safety and tolerability continued to be favorable with no new or worsening safety findings. Overall, the efficacy and safety outcomes in the Japanese subgroup were comparable with the ASCEMBL global study population, which supports the use of asciminib in Japanese patients with previously treated CML-CP.

Keywords: ABL1 inhibitor; Asciminib; BCR; Chronic myeloid leukemia; Major molecular response; STAMP; Tyrosine kinase inhibitors.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aniline Compounds / therapeutic use
  • East Asian People
  • Female
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Japan
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myeloid, Chronic-Phase / drug therapy
  • Male
  • Middle Aged
  • Niacinamide / analogs & derivatives
  • Nitriles / therapeutic use
  • Pyrazoles
  • Quinolines / therapeutic use
  • Treatment Outcome
  • Tyrosine Kinase Inhibitors* / therapeutic use

Substances

  • Aniline Compounds
  • asciminib
  • bosutinib
  • Fusion Proteins, bcr-abl
  • Niacinamide
  • Nitriles
  • Pyrazoles
  • Quinolines
  • Tyrosine Kinase Inhibitors