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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: The Case for the Use of Dasatinib or Nilotinib in First-line Therapy


The Case for the Use of Dasatinib or Nilotinib in First-line Therapy

Although imatinib is an excellent drug based on the IRIS data, the Hammersmith data and the study by Lucas et al.[7] suggest that long-term results are not as favorable. Based on the Hammersmith data, roughly one-third of patients will not have the response that one would hope for. The data reported by Lucas et al.[7] suggest that only approximately half of the patients treated with imatinib in a community setting would be expected to have a sustained positive outcome. Imatinib is generally well tolerated. Certainly, if it is compared with IFN-α, then its side-effect profile is very favorable. However, although most of its nonhematologic side effects are grade 1 or 2, they could significantly affect quality of life in the long run. For instance, if given the choice, most patients would certainly want to avoid a lifetime of grade 1/2 diarrhea.

The most important argument in favor of using dasatinib or nilotinib in first-line therapy is the fact that with both agents, the response milestones (CCyR and MMR) are achieved earlier and in more patients than with imatinib. Long-term follow-up data clearly show that patients who achieve these milestones earlier have the best outcomes. The IRIS data suggest that once a TKI is started, there is a window of 2 to 3 years during which the risk of disease progression or transformation is highest. The ENESTnd and DASISION studies strongly suggest that nilotinib and dasatinib decrease the risk of disease progression, certainly up to the point of analysis. This outcome is not unexpected, because they have a broader spectrum of activity as far as resistance- imparting mutations are concerned. Although a blast transformation has become a relatively rare event in the TKI era, this outcome is devastating for patients. Casting a wider net with dasatinib or nilotinib to diminish the risk of disease progression early on is certainly a sound strategy. These agents do not have the track record of sustained response that imatinib has. Technically, one cannot extrapolate to dasatinib and nilotinib the observations on the 2- to 3-year “window of opportunity” that have been made with imatinib. However, currently no data suggest that they would not be similar in that respect. Finally, based on available data, one could predict that fewer patients started on dasatinib or nilotinib will require salvage therapy than those started on imatinib.