Faderl S, Talpaz M, Estrov Z, et al. The biology of chronic myeloid leukemia. N Engl J Med 1999;341:164–172.
SEER Stat Fact Sheets: Chronic Myeloid Leukemia. National Cancer Institute Surveillance Epidemiology and End Results Web site. Available at: http://seer.cancer.gov/statfacts/html/cmyl.html. Accessed November 30, 2011.
O’Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic phase chronic myeloid leukemia. N Engl J Med 2003;348:994–1004.
Hochhaus A, O’Brien SG, Guilhot F, et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 2009;23:1054–1061.
Deininger M, O’Brien SG, Guilhot F, et al. International randomized study of interferon vs STI571 (IRIS) 8-year follow up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with imatinib [abstract]. Blood 2009;114:462. Abstract 1126.
de Lavallade H, Apperley JF, Khorashad JS, et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol 2008;26:3358–3363.
Lucas CM, Wang L, Austin GM, et al. A population study of imatinib in chronic myeloid leukaemia demonstrates lower efficacy than in clinical trials. Leukemia 2008;22:1963–1966.
Cortes JE, Baccarani M, Guilhot F, et al. Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular end points: tyrosine kinase inhibitor optimization and selectivity study. J Clin Oncol 2010;28:424–430.
Hehlmann R, Lauseker M, Jung-Munkwitz S, et al. Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-{alpha} in newly diagnosed chronic myeloid leukemia. J Clin Oncol 2011;29:1634–1642.
Preudhomme C, Guilhot J, Nicolini FE, et al. Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med 2010;363:2511–2521.
Rosti G, Palandri F, Castagnetti F, et al. Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia. Blood 2009;114:4933–4938.
Cortes JE, Jones D, O’Brien S, et al. Nilotinib as front-line treatment for patients with chronic myeloid leukemia in early chronic phase. J Clin Oncol 2010;28:392–397.
Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251–2259.
Hochhaus A, Saglio G, le Coutre P, et al. Superior efficacy of nilotinib compared with imatinib in newly-diagnosed patients with chronic myeloid leukemia in chronic (CML-CP): ENESTnd minimum 24-month follow-up [abstract]. Haematologica 2011;96(Suppl 2):Abstract 0484.
Hughes TP, Hochhaus A, Saglio G, et al. ENESTnd update: continued superiority of nilotinib versus imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) [abstract]. Blood 2010;116:Abstract 207.
Cortes JE, Jones D, O’Brien S, et al. Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia. J Clin Oncol 2010;28:398–404.
Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010;362:2260–2270.
Hochhaus A, Shah N, Cortes J, et al. Efficacy and safety of dasatinib compared with imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): minimum 24-month follow-up from the DASISION trial [abstract]. Haematologica 2011;96(Suppl 2):Abstract 1011.
Quintás-Cardama A, Kantarjian H, O’Brien S, et al. Pleural effusion in patients with chronic myelogenous leukemia treated with dasatinib after imatinib failure. J Clin Oncol 2007;25:3908–3914.
Shah NP, Kantarjian HM, Kim DW, et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol 2008;26:3204–3212.
Porkka K, Baccarani M, Cortes J, et al. Pleural effusion in patients with chronic-phase chronic myeloid leukemia (CML-CP) who received first-line dasatinib in the DASISION trial: patient characteristics, management, and outcomes [abstract]. Haematologica 2011;96(Suppl 2):Abstract 0692.
Radich JP, Kopecky KJ, Kamel-Reid S, et al. A randomized phase II trial of dasatinib 100 mg vs imatinib 400 mg in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): the S0325 intergroup trial [abstract]. Blood 2010;116:Abstract LBA6.
Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006;355:2408–2417.
Baccarani M, Guilhot F, Larson RA, et al. Outcomes by cytogenetic and molecular response at 12 and 18 months of imatinib in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP) in the IRIS trial [abstract]. Blood 2006;108:606a. Abstract 2138.
Weisberg E, Manley PW, Breitenstein W, et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 2005;7:129–141.
Tokarski JS, Newitt JA, Chang CY, et al. The structure of dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants. Cancer Res 2006;66:5790–5797.
O’Hare T, Walters DK, Stoffregen EP, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res 2005;65:4500–4505.
Apperley JF. Part I: mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol 2007;8:1018–1029.
Kreutzman A, Juvonen V, Kairisto V, et al. Mono/oligoclonal T- and NK-cells are common in chronic myeloid leukemia patients at diagnosis and expand during dasatinib therapy. Blood 2010;116:772–782.
Nagata Y, Ohashi K, Fukuda S, et al. Clinical features of dasatinib-induced large granular lymphocytosis and pleural effusion. Int J Hematol 2010;91:799–807.
Mustjoki S, Ekblom M, Arstila TP, et al. Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy. Leukemia 2009;23:1398–1405.
Kim DH, Kamel-Reid S, Chang H, et al. Natural killer or natural killer/T cell lineage large granular lymphocytosis associated with dasatinib therapy for Philadelphia chromosome positive leukemia. Haematologica 2009;94:135–139.
Schiffer CA, Cortes JE, Saglio G, et al. Association of lymphocytosis following treatment with dasatinib with response and outcome [abstract]. J Clin Oncol 2010;28(15 Suppl):Abstract 6553.
Schiffer CA, Cortes JE, Saglio G, et al. Lymphocytosis following first-line treatment for CML in chronic phase with dasatinib is associated with improved responses: a comparison with imatinib [abstract]. Blood 2010;116:Abstract 358.
O’Brien S, Berman E, Moore JO, et al. NCCN Task Force Report: tyrosine kinase inhibitor therapy selection in the management of patients with chronic myelogenous leukemia. J Natl Compr Canc Netw 2011:9(Suppl 2):S1–25.

As an organization accredited by the ACCME, Medscape, LLC, requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.

Medscape, LLC, encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.

Author

Paul J. Shami, MD

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

Disclosures

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

Editor

Kerrin M. Green, MA

Assistant Managing Editor, Journal of the National Comprehensive Cancer Network

Disclosures

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

CME Author(s)

Laurie Barclay, MD

Freelance writer and reviewer, Medscape, LLC

Disclosures

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

CME Reviewer(s)

Nafeez Zawahir, MD

CME Clinical Director, Medscape, LLC

Disclosures

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

Sarah Fleischman

CME Program Manager, Medscape, LLC

Disclosures

Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.

CME

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
THIS ACTIVITY HAS EXPIRED FOR CREDIT
Valid for credit through: 1/6/2013, 11:59 PM EST

Start Activity

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:

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

Disclosures

Author

Paul J. Shami, MD

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

Disclosures

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

Editor

Kerrin M. Green, MA

Assistant Managing Editor, Journal of the National Comprehensive Cancer Network

Disclosures

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

CME Author(s)

Laurie Barclay, MD

Freelance writer and reviewer, Medscape, LLC

Disclosures

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

CME Reviewer(s)

Nafeez Zawahir, MD

CME Clinical Director, Medscape, LLC

Disclosures

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

Sarah Fleischman

CME Program Manager, Medscape, LLC

Disclosures

Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.

Accreditation Statements

For Physicians

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and JNCCN - The Journal of the National Comprehensive Cancer Network. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians.

Medscape, LLC designates this Journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Medscape, LLC staff have disclosed that they have no relevant financial relationships.

Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page. To receive AMA PRA Category 1 Credit™, you must receive a minimum score of 70% on the post-test.

Follow these steps to earn CME/CE credit*:

Read the target audience, learning objectives, and author disclosures.
Study the educational content online or printed out.
Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. Medscape Education encourages you to complete the Activity Evaluation to provide feedback for future programming.

You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.

*The credit that you receive is based on your user profile.

processing....

The Case for the Use of Imatinib in First-line Therapy

Imatinib is clearly a very active drug. One can therefore make a strong argument to continue using it in the first-line setting. Imatinib has been approved for 10 years, and most patients who were started on it in the first-line setting are alive and doing well. Therefore, imatinib has a proven track record for a sustained response lasting at least several years. Dasatinib and nilotinib do not have such a long track record. Furthermore, imatinib is generally well tolerated. Most of its nonhematologic side effects, such as diarrhea and peripheral edema, are of grade 1 or 2. Finally, with proper monitoring of disease response using current molecular techniques, one should be able to identify patients with loss of response early on and switch them to dasatinib or nilotinib. Similar to imatinib, the latter agents are not active against the T315I mutation, for which an allogeneic stem cell transplant is still the preferred treatment until agents with an even broader spectrum of activity are approved.

« Back

Page 3 of 5

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

CME Information

Abstract and Introduction
The Facts
The Case for the Use of Imatinib in First-line Therapy
The Case for the Use of Dasatinib or Nilotinib in First-line Therapy
What To Do?

References

CME

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

Target Audience and Goal Statement

Disclosures

Author

Paul J. Shami, MD

Editor

Kerrin M. Green, MA

CME Author(s)

Laurie Barclay, MD

CME Reviewer(s)

Nafeez Zawahir, MD

Sarah Fleischman