Varying concentrations of tyrosine kinase inhibitors in chronic myeloid leukemia patients following bariatric surgery: a case series

Ann Hematol. 2024 Nov;103(11):4765-4771. doi: 10.1007/s00277-024-05924-4. Epub 2024 Aug 12.

Abstract

Bariatric surgery is increasingly performed to treat severe obesity. As a result of anatomical and physiological changes in the gastrointestinal tract, the pharmacokinetics (PK) of oral drugs can be altered, affecting their efficacy and safety. This includes the class of tyrosine kinase inhibitors (TKIs) which are used to treat chronic myeloid leukemia (CML). This case series describes the clinical course of four CML cases with a history of bariatric surgery. The patients used various TKIs (nilotinib, dasatinib, bosutinib, ponatinib, and imatinib) for which 15 drug levels were measured. The measured TKI concentrations were in part subtherapeutic, and highly variable when compared to mean levels measured in the general population. Multiple drug levels were measured in these patients, as the clinicians were aware of the possible impact of bariatric surgery. The drug levels were used as additional input for clinical decision-making. All four patients required TKI switches and/or dose modifications to achieve an effective and tolerable treatment. Eventually, adequate clinical and molecular remissions were achieved in all cases. In summary, TKI concentrations of patients undergoing bariatric surgery may be subtherapeutic. Moreover, there is substantial interindividual and intraindividual variation, which may be explained by the complex interference of bariatric surgery and associated weight loss. For clinical practice, therapeutic drug monitoring is advised in patients with a history of bariatric surgery in case of suboptimal response or loss of response.

Keywords: Bariatric surgery; Chronic myeloid leukemia; Pharmacokinetics; Roux-en-Y gastric bypass; Sleeve gastrectomy; Therapeutic drug monitoring; Tyrosine kinase inhibitors.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aniline Compounds / pharmacokinetics
  • Aniline Compounds / therapeutic use
  • Bariatric Surgery*
  • Dasatinib / therapeutic use
  • Female
  • Humans
  • Imatinib Mesylate / pharmacokinetics
  • Imatinib Mesylate / therapeutic use
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacokinetics
  • Imidazoles / therapeutic use
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Male
  • Middle Aged
  • Nitriles
  • Obesity, Morbid / surgery
  • Protein Kinase Inhibitors* / administration & dosage
  • Protein Kinase Inhibitors* / pharmacokinetics
  • Protein Kinase Inhibitors* / therapeutic use
  • Pyridazines / administration & dosage
  • Pyridazines / pharmacokinetics
  • Pyridazines / therapeutic use
  • Pyrimidines
  • Quinolines
  • Tyrosine Kinase Inhibitors

Substances

  • Protein Kinase Inhibitors
  • Imatinib Mesylate
  • Dasatinib
  • Aniline Compounds
  • nilotinib
  • Imidazoles
  • Pyridazines
  • bosutinib
  • Tyrosine Kinase Inhibitors
  • Nitriles
  • Pyrimidines
  • Quinolines