Concomitant Administration of Direct Oral Anticoagulants in Chronic Phase Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors

Clin Drug Investig. 2020 Dec;40(12):1177-1181. doi: 10.1007/s40261-020-00980-w. Epub 2020 Oct 22.

Abstract

Background and objective: In the last decades, the chronic myeloid leukemia (CML) therapeutic landscape has changed dramatically with the introduction of tyrosine kinase inhibitors (TKIs), with 10-year survival rates improving to up to 80%. Long-lasting TKI treatment, in particular with second-generation TKIs, has enabled clinicians to manage the onset of several side effects and other co-morbidities, such as atrial fibrillation or venous thromboembolism (VTE).

Methods: We retrospectively evaluated nine CML patients treated with TKIs between 2017 and 2020 who experienced atrial fibrillation or VTE and received concomitant administration of TKIs and direct oral anticoagulants (DOACs) outside clinical trials, to evaluate the efficacy and safety of this combination.

Results: Median age was 66 years at CML diagnosis (range 52-73 years) and 69 years at the time of starting DOACs. A female predominance was observed. The median follow-up of concomitant DOAC and TKI administration was 8.5 months; edoxaban was administered in six patients and apixaban in two patients, and one patient received rivaroxaban. Regarding CML treatment, four patients received imatinib, two patients bosutinib, and three nilotinib. In eight patients DOACs were started for atrial fibrillation and in one patient for VTE. In none of the patients treated with the combination were additional symptomatic thrombotic adverse events or major bleedings reported.

Conclusion: In this small case series, the use of DOACs in CML patients seemed feasible. Additional data on long-term outcomes including a larger cohort of CML patients treated with DOACs are, however, needed.

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aniline Compounds
  • Anticoagulants / therapeutic use*
  • Cohort Studies
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Imatinib Mesylate / therapeutic use*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Male
  • Middle Aged
  • Nitriles
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines
  • Quinolines
  • Retrospective Studies
  • Venous Thromboembolism

Substances

  • Aniline Compounds
  • Anticoagulants
  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Quinolines
  • bosutinib
  • Imatinib Mesylate
  • nilotinib