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How to Choose Frontline Therapy for Chronic Myelogenous Leukemia: So Many Drugs, Not So Many Patients

  • Authors: Paul J. Shami, MD
  • CME Released: 1/6/2012
  • Valid for credit through: 1/6/2013, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for primary care clinicians, hematologists, oncologists, and other healthcare professionals caring for patients with CML.

The goal of this activity is to describe first-line therapy of CML using TKIs based on a review.

Upon completion of this activity, participants will be able to:

  1. Describe similarities and differences of imatinib, nilotinib, and dasatinib, based on a review
  2. Describe the case for the use of imatinib in first-line therapy of CML, based on a review
  3. Describe the case for the use of dasatinib or nilotinib in first-line therapy of CML, based on a review


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  • Paul J. Shami, MD

    Division of Hematology and Hematologic Malignancies, University of Utah, Huntsman Cancer Institute, Salt Lake City, Utah


    Disclosure: Paul J. Shami, MD, has disclosed the following relevant financial relationships:
    Serves on advisory boards and a speaker’s bureau for: Novartis Pharmaceuticals Corporation


  • Kerrin M. Green, MA

    Assistant Managing Editor, Journal of the National Comprehensive Cancer Network


    Disclosure: Kerrin M. Green, MA, has disclosed no relevant financial relationships.

CME Author(s)

  • Laurie Barclay, MD

    Freelance writer and reviewer, Medscape, LLC


    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

CME Reviewer(s)

  • Nafeez Zawahir, MD

    CME Clinical Director, Medscape, LLC


    Disclosure: Nafeez Zawahir, MD, has disclosed no relevant financial relationships.

  • Sarah Fleischman

    CME Program Manager, Medscape, LLC


    Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.

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How to Choose Frontline Therapy for Chronic Myelogenous Leukemia: So Many Drugs, Not So Many Patients

Authors: Paul J. Shami, MDFaculty and Disclosures

CME Released: 1/6/2012

Valid for credit through: 1/6/2013, 11:59 PM EST


Abstract and Introduction


With the development of tyrosine kinase inhibitors (TKIs), the management and outlook for patients with chronic myelogenous leukemia (CML) have completely changed over the past 10 years. Imatinib was the first TKI approved to treat CML in the chronic phase. After their initial approval as second-line agents, dasatinib and nilotinib were compared with imatinib in the first-line setting in 2 randomized trials. Both trials showed that therapeutic milestones (complete cytogenetic remission and major molecular remission) occurred earlier with these newer agents, leading to their approval for the treatment of newly diagnosed CML. Therefore, 3 different TKIs are now available for treating CML. Long-term follow-up of patients treated with imatinib shows that the attainment of therapeutic milestones by 12 months of therapy leads to better long-term outcomes. Most patients who experience disease progression on imatinib do so within the first 3 years of therapy. Therefore, one can argue that dasatinib or nilotinib should be chosen to treat patients with newly diagnosed CML. However, these agents do not have the long-term track record of imatinib. This article summarizes the published data and reviews the rationale in choosing the appropriate TKI for first-line treatment of CML in the chronic phase. (JNCCN 2012;10:112–119)


Chronic myelogenous leukemia (CML) is a myeloproliferative disorder resulting from a translocation between chromosomes 9 and 22 (t(9;22) or Philadelphia chromosome) leading to an abnormal fusion protein (BCR-ABL) with dysregulated tyrosine kinase activity.[1] Without therapy, CML has a predictable progression from a chronic phase (CP) to the more advanced accelerated (AP) and blast (BP) phases. Although it is a rare disease, with an estimated incidence of 4870 in the United States in 2010,[2] it has occupied a substantial portion of the medical literature over the past 10 years because of the development of highly successful tyrosine kinase inhibitors (TKIs) that have changed the treatment paradigm. In fact, attempts to follow a similar strategy for other malignancies has become the main focus of cancer drug development, although with less spectacular results. Three TKIs have received regulatory approval to treat CML. Imatinib was the first agent to be approved, and established a change in the standard of care. Dasatinib and nilotinib were then developed as second-line agents for imatinib failures. They are both active against most ABL tyrosine kinase domain mutations that impart resistance to imatinib. As expected, the second-generation TKIs were ultimately tested in the first-line setting and have now received regulatory approval for that indication. This article reviews the data on the drugs to determine the best approach to choosing a first-line agent for patients with CP-CML.