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Second-Line TKIs Offer Expanded Treatment Options for Newly Diagnosed Patients with CML

New first-line therapies for patients with CML highlight notable updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) for CML at the National Comprehensive Cancer Network® (NCCN®) 16th Annual Conference.

HOLLYWOOD, FL — Second generation tyrosine kinase inhibitor (TKI) therapies approved for first-line therapy of chronic myelogenous leukemia (CML) offer newly diagnosed patients an expanded range of treatment options, according to Susan O’Brien, MD, of The University of Texas MD Anderson Cancer Center and chair of the NCCN Guidelines™ for CML. Dr. O’Brien emphasized the considerable advances made in the treatment of CML during her presentation of the updated NCCN Guidelines for CML at the NCCN 16th Annual Conference on March 11, 2011.

The addition of nilotinib (Tasigna®, Novartis Oncology) and dasatinib (SPRYCEL®, Bristol-Myers Squibb) as primary treatment options for patients with CML are the most significant updates to the NCCN Guidelines for CML, noted Dr. O’Brien. The newly approved therapies join the current standard of care, imatinib (Gleevec®, Novartis Oncology) as frontline options for newly diagnosed patients.

“The development of imatinib revolutionized the treatment of CML, providing patients with a safe and effective treatment option associated with an excellent survival benefit,” said Dr. O’Brien.

However, in recent studies, dasatinib and nilotinib were associated with significantly higher response rates and reduction in the 12-month incidence of accelerated or blast phase in patients with CML. Subsequently, the FDA granted approval of dasatinib and nilotinib as a first line therapy for newly diagnosed patients with CML. Both drugs were previously reserved for use in patients with resistance or intolerance to prior therapy, including imatinib.

“For newly diagnosed patients, all three TKI’s recommended in the NCCN Guidelines are viable treatment options,” said Dr. O’Brien. “Selection of appropriate TKI therapy will depend on the stage of the disease, the agent’s side effect profile and its relative effectiveness against BCR-ABL mutations.”

In terms of monitoring response to therapy, Dr. O’Brien noted that complete cytogenetic response (CyCR) remains the gold standard, although patients who rapidly achieve a major molecular response (MMR) also have a low rate of relapse.

“Research has shown that patients who achieve a complete cytogenetic response live longer, whereas a molecular response has not been shown to improve survival. Patients who do not achieve a complete molecular response should not be considered to have failed treatment,” clarified Dr. O’Brien.

There are clinical trials currently underway to determine if complete molecular response offers hope for treatment discontinuation or may be helpful in predicting future risk of progression or relapse.

In addition to the newly approved therapies, there are also several agents in clinical trials with promising activity.

Dr. O’Brien touched upon two TKIs, including ponatinib (ARIAD Pharmaceuticals), which has demonstrated efficacy in treating patients with the treatment-resistant T3151 mutation, and bosutinib (Pfizer), which has shown efficacy as a first-, second-, and third-line treatment.

“Availability of more potent TKIs has widened the treatment options and, given the new agents in the pipeline, the outlook for patients with CML continues to look promising,” said Dr. O’Brien.

The NCCN Guidelines are developed and updated through an evidence-based process with explicit review of the scientific evidence integrated with expert judgment by multidisciplinary panels of expert physicians from NCCN Member Institutions. The most recent version of this and all the NCCN Guidelines are available free of charge at

About the National Comprehensive Cancer Network

The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 27 leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The primary goal of all NCCN initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so patients can live better lives. For more information, visit

The NCCN Member Institutions are:

  • Fred & Pamela Buffett Cancer Center
  • Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
  • City of Hope Comprehensive Cancer Center
  • Dana-Farber/Brigham and Women's Cancer Center | Massachusetts General Hospital Cancer Center
  • Duke Cancer Institute
  • Fox Chase Cancer Center
  • Huntsman Cancer Institute at the University of Utah
  • Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
  • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
  • Mayo Clinic Cancer Center
  • Memorial Sloan Kettering Cancer Center
  • Moffitt Cancer Center
  • The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
  • Roswell Park Comprehensive Cancer Center
  • Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
  • St. Jude Children's Research Hospital/The University of Tennessee Health Science Center
  • Stanford Cancer Institute
  • University of Alabama at Birmingham Comprehensive Cancer Center
  • UC San Diego Moores Cancer Center
  • UCSF Helen Diller Family Comprehensive Cancer Center
  • University of Colorado Cancer Center
  • University of Michigan Rogel Cancer Center
  • The University of Texas MD Anderson Cancer Center
  • University of Wisconsin Carbone Cancer Center
  • Vanderbilt-Ingram Cancer Center
  • Yale Cancer Center/Smilow Cancer Hospital