Rotation of nilotinib and imatinib for first-line treatment of chronic phase chronic myeloid leukemia

Am J Hematol. 2016 Jun;91(6):617-22. doi: 10.1002/ajh.24362. Epub 2016 Apr 24.

Abstract

The introduction of second-generation tyrosine-kinase inhibitors (TKIs) has generated a lively debate on the choice of first-line TKI in chronic phase, chronic myeloid leukemia (CML). Despite the TKIs have different efficacy and toxicity profiles, the planned use of two TKIs has never been investigated. We report on a phase 2 study that was designed to evaluate efficacy and safety of a treatment alternating nilotinib and imatinib, in newly diagnosed BCR-ABL1 positive, chronic phase, CML patients. One hundred twenty-three patients were enrolled. Median age was 56 years. The probabilities of achieving a complete cytogenetic response, a major molecular response, and a deep molecular response (MR 4.0) by 2 years were 93%, 87%, and 61%, respectively. The 5-year overall survival and progression-free survival were 89%. Response rates and survival are in the range of those reported with nilotinib alone. Moreover, we observed a relatively low rate of cardiovascular adverse events (5%). These data show that the different efficacy and toxicity profiles of TKIs could be favorably exploited by alternating their use. Am. J. Hematol. 91:617-622, 2016. © 2016 Wiley Periodicals, Inc.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases / chemically induced
  • Drug Administration Schedule
  • Female
  • Humans
  • Imatinib Mesylate / administration & dosage*
  • Imatinib Mesylate / adverse effects
  • Leukemia, Myeloid, Chronic-Phase / complications
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / mortality
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Survival Analysis
  • Survival Rate
  • Treatment Outcome
  • Young Adult

Substances

  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • nilotinib