Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia: primary results of the phase 4 BYOND study

Leukemia. 2020 Aug;34(8):2125-2137. doi: 10.1038/s41375-020-0915-9. Epub 2020 Jun 22.

Abstract

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of cumulative confirmed major cytogenetic response (MCyR) rate by 1 year was 75.8% in Ph+ CP CML patients after one or two prior TKIs and 62.2% after three prior TKIs. Cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) rates by 1 year were 80.6% and 70.5%, respectively, in Ph+ CP CML patients overall. No patient progressed to AP/BP on treatment. Across all patients, the most common treatment-emergent adverse events were diarrhea (87.7%), nausea (39.9%), and vomiting (32.5%). The majority of patients had confirmed MCyR by 1 year and MMR by 1 year, further supporting bosutinib use for Ph+ CP CML patients resistant/intolerant to prior TKIs.

Publication types

  • Clinical Trial, Phase IV
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aniline Compounds / adverse effects
  • Aniline Compounds / therapeutic use*
  • Female
  • Humans
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / genetics
  • Leukemia, Myeloid, Chronic-Phase / psychology
  • Male
  • Middle Aged
  • Nitriles / adverse effects
  • Nitriles / therapeutic use*
  • Philadelphia Chromosome
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Quality of Life
  • Quinolines / adverse effects
  • Quinolines / therapeutic use*

Substances

  • Aniline Compounds
  • Nitriles
  • Protein Kinase Inhibitors
  • Quinolines
  • bosutinib
  • Protein-Tyrosine Kinases

Associated data

  • ClinicalTrials.gov/NCT02228382