Tyrosine kinase inhibitors in Ph+ acute lymphoblastic leukaemia: facts and perspectives

Ann Hematol. 2016 Apr;95(5):681-93. doi: 10.1007/s00277-016-2617-y. Epub 2016 Feb 19.

Abstract

Two tyrosine kinase inhibitors (TKIs), imatinib and dasatinib, are registered for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) in adults. Other two TKIs (nilotinib and ponatinib) have been tested in the second-line, can offer an alternative in the patients who fail the first-line, and can acquire a role also in the first-line. Here, we provide a summary of the reports of TKIs, used alone, and in combination with chemotherapy. TKIs are very effective alone and with corticosteroids and are likely to improve substantially the outcome when they are combined with standard or dose-adapted chemotherapy. While the complete haematologic remission rate is always very high, close to 100 %, the cytogenetic and molecular remission rates are lower, so that TKIs are still considered as a complement to chemotherapy and as a bridge to allogeneic stem cell transplantation (allo-SCT). However, many patients relapse before transplant, and many patients still relapse, even if they have been submitted to allo-SCT. A proper use of TKIs, the introduction of ponatinib, and of "new generation" TKIs should improve further on the outcome of Ph+ ALL.

Keywords: Acute lymphoblastic leukaemia; Philadelphia chromosome; Target therapy; Tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage
  • Adult
  • Age Factors
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Fusion Proteins, bcr-abl / antagonists & inhibitors*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Middle Aged
  • Molecular Targeted Therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / enzymology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Prospective Studies
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Therapies, Investigational
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Fusion Proteins, bcr-abl