Efficacy and safety of bosutinib in previously treated patients with chronic myeloid leukemia: final results from the BYOND trial

Leukemia. 2024 Oct;38(10):2162-2170. doi: 10.1038/s41375-024-02372-x. Epub 2024 Aug 20.

Abstract

This final analysis from the phase 4 BYOND trial reports outcomes with bosutinib in patients with previously treated chronic myeloid leukemia (CML); 163 patients with CML resistant/intolerant to previous tyrosine kinase inhibitors received bosutinib (starting dose: 500 mg QD). At study completion (median follow-up, 47.8 months), 48.1% (n = 75/156) of patients with Philadelphia chromosome-positive chronic phase CML were still receiving treatment. Among evaluable patients, 71.8% (95% CI, 63.9-78.9) and 59.7% (95% CI, 51.4-67.7) attained or maintained major molecular response (MMR) and molecular response (MR)4, respectively, at any time on treatment. The majority of patients achieved a deeper molecular response relative to baseline while on bosutinib. Kaplan-Meier probabilities (95% CI) of maintaining MMR and MR4 at 36 months were 87.2% (78.0-92.7) and 80.7% (69.4-88.1), respectively. At 48 months, the Kaplan-Meier overall survival rate was 88.3% (95% CI, 81.8-92.6); there were 17 deaths, including 2 that were considered CML related. Long-term adverse events (AEs) were consistent with the known safety profile of bosutinib, and no new safety issues were identified. The management of AEs through dose reduction maintained efficacy while improving tolerability. These results support the use of bosutinib in patients with previously treated CML.ClinicalTrials.gov, NCT02228382.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aniline Compounds* / administration & dosage
  • Aniline Compounds* / adverse effects
  • Aniline Compounds* / therapeutic use
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Follow-Up Studies
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / mortality
  • Male
  • Middle Aged
  • Nitriles* / administration & dosage
  • Nitriles* / adverse effects
  • Nitriles* / therapeutic use
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Quinolines* / administration & dosage
  • Quinolines* / adverse effects
  • Quinolines* / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • bosutinib
  • Aniline Compounds
  • Nitriles
  • Quinolines
  • Protein Kinase Inhibitors

Associated data

  • ClinicalTrials.gov/NCT02228382