Nilotinib as frontline and second-line therapy in chronic myeloid leukemia: open questions

Crit Rev Oncol Hematol. 2012 Jun;82(3):370-7. doi: 10.1016/j.critrevonc.2011.08.002. Epub 2011 Sep 7.


Nilotinib is a second generation ABL tyrosine kinase inhibitor (TKI) that exerts major anti-leukemic effects in newly diagnosed patients with chronic myeloid leukemia (CML) as well as in most patients with imatinib-resistant CML. In freshly diagnosed patients, the anti-leukemic activity of nilotinib exceeds the efficacy of imatinib, and although long-term data for nilotinib are not available yet, the drug has recently been approved for firstline treatment of chronic phase CML in various countries. Still however, several questions concerning the optimal dose, follow-up parameters, long-term safety, and patient selection remain open. Likewise, it remains uncertain whether both Sokal low-risk and high-risk patients should receive nilotinib as frontline therapy in the future. Another question is whether nilotinib can completely eradicate CML in a subset of patients. Furthermore, it remains unclear whether and what comorbidity must be regarded as relative or absolute contra-indication for this TKI. To discuss these issues, the Austrian CML Working Group organized a series of meetings in 2010. In the current article, the outcomes from these discussions are summarized and presented together with recommendations for frontline use of TKIs in various groups of patients with CML. These recommendations should assist in daily practice as well as in the preparation and conduct of clinical trials.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Cerebrovascular Disorders / drug therapy*
  • Cerebrovascular Disorders / epidemiology
  • Cerebrovascular Disorders / pathology
  • Clinical Trials as Topic
  • Comorbidity
  • Contraindications
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / pathology
  • Drug Administration Schedule
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / metabolism
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / epidemiology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Patient Selection
  • Piperazines / administration & dosage
  • Piperazines / therapeutic use
  • Practice Guidelines as Topic
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism
  • Pyrimidines / administration & dosage
  • Pyrimidines / therapeutic use*
  • Treatment Outcome


  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl
  • nilotinib