Clinical roundtable monograph: Emerging treatment options for TKI-resistant chronic myelogenous leukemia.

Jorge Cortes, Jerald Radich, Michael J. Mauro

Research output: Contribution to journalArticle

Abstract

The development of tyrosine kinase inhibitors (TKIs) that inhibit signaling of the constitutive BCR-ABL protein revolutionized the treatment of chronic myelogenous leukemia (CML). These agents have dramatically changed the treatment landscape for CML, shifting the use of allogeneic stem cell transplantation to selected patients in the salvage setting. Four BCR-ABL TKIs are now commercially available for the treatment of CML: the first-generation TKI imatinib, and the second-generation TKIs dasatinib, nilotinib, and bosutinib. Continuous treatment with these agents induces durable responses in a high proportion of patients with chronic-phase CML. Research is focused on identifying which patients can discontinue therapy without a recurrence of disease. For the group of patients with resistance to TKIs, multiple alternative therapies are being evaluated. The third-generation TKI ponatinib is a BCR-ABL inhibitor that has demonstrated significant activity, including in patients with the TKI resistance mutation T315I. The homoharringtonine derivative omacetaxine mepesuccinate, which inhibits protein synthesis, has also demonstrated clinical activity in CML, including in patients with TKI resistance due to T315I and in patients who have TKI resistance despite no evidence of ABL mutations. It is essential that clinicians implement these new agents with care and change therapies only when appropriate in order to preserve as many options as possible for future use if needed.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalClinical advances in hematology & oncology : H&O
Volume10
Issue number10 Suppl 19
StatePublished - Oct 2012
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Therapeutics
Leukemia, Myeloid, Chronic Phase
Mutation
Stem Cell Transplantation
Complementary Therapies
Proteins
Recurrence
Research

ASJC Scopus subject areas

  • Hematology
  • Oncology

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Clinical roundtable monograph : Emerging treatment options for TKI-resistant chronic myelogenous leukemia. / Cortes, Jorge; Radich, Jerald; Mauro, Michael J.

In: Clinical advances in hematology & oncology : H&O, Vol. 10, No. 10 Suppl 19, 10.2012, p. 1-16.

Research output: Contribution to journalArticle

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