Seminars in Hematology
Volume 46 , Pages S11-S15 , April 2009

Clinical Strategies to Achieve an Early and Successful Response to Tyrosine Kinase Inhibitor Therapy

  • Timothy Hughes

      Affiliations

    • Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, Australia
    • Corresponding Author InformationAddress correspondence to Timothy Hughes, MD, Deputy Head, Division of Haematology, Institute of Medical and Veterinary Science, Frome Road, Adelaide, SA, 5000, Australia
    • ,
  • Andreas Hochhaus

      Affiliations

    • Abteilung Leukämieforschung, III Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany

References 

  1. Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;108:1809–1820
  2. O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, 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
  3. Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–2417
  4. Hughes TP, Kaeda J, Branford S, Rudzki Z, Hochhaus A, Hensley ML, et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med. 2003;349:1423–1432
  5. 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. In press.
  6. Guilhot F, Larson RA, O'Brien SG, Gathmann I, Druker BJ. Time to complete cytogenetic response (CCyR) does not affect long-term outcomes for patients on imatinib therapy. Blood. 2007;110:16a
  7. Branford S, Seymour JF, Grigg A, Arthur C, Lynch K, Hughes T. Increasing frequency and marked stability of complete molecular response is observed in imatinib-treated CML patients with long-term follow up. Blood. 2006;108:131a
  8. Druker BJ, Gathmann I, Bolton AE, Larson RA. Probability and impact of obtaining a cytogenetic response to imatinib as initial therapy for chronic myeloid leukemia (CML) in chronic phase. Blood. 2003;102:182a
  9. Aoki E, Kantarjian H, O'Brien S, Talpaz M, Giles F, Garcia-Manero G, et al. High-dose imatinib mesylate treatment in patients (pts) with untreated early chronic phase (CP) chronic myeloid leukemia (CML): 2.5-year follow-up. J Clin Oncol. 2006;24:345s
  10. Kantarjian H, Talpaz M, O'Brien S, Garcia-Manero G, Verstovsek S, Giles F, et al. High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. Blood. 2004;103:2873–2878
  11. Baccarani M, Castagnetti F, Porkka K. A prospective study of imatinib 400 mg vs 800 mg as a front-line therapy in Sokal high risk Ph+ chronic myeloid leukemia patients. Haematologica. 2008;93(Suppl 1):161–162
  12. Cortes JE, Baccarani M, Guilhot F, Druker BJ, Yu R, Rudoltz M, et al. First report of the TOPS study: a randomized phase III trial of 400 mg vs 800 mg imatinib in patients with newly diagnosed, previously untreated CML in chronic phase using molecular endpoints. Haematologica. 2008;93(Suppl 1):160–161
  13. Larson RA, Druker BJ, Guilhot FA, O'Brien SG, Riviere GJ, Krahnke T, et al. Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood. 2008;111:4022–4028
  14. Picard S, Titier K, Etienne G, Teilhet E, Ducint D, Bernard MA, et al. Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood. 2007;109:3496–3499
  15. Thomas J, Wang L, Clark RE, Pirmohamed M. Active transport of imatinib into and out of cells: implications for drug resistance. Blood. 2004;104:3739–3745
  16. White DL, Saunders VA, Dang P, Engler J, Venables A, Zrim S, et al. Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: higher doses of imatinib may overcome the negative impact of low OCT-1 activity. Blood. 2007;110:4064–4072
  17. Kantarjian HM, Talpaz M, O'Brien S, Giles F, Garcia-Manero G, Faderl S, et al. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood. 2003;101:473–475
  18. Kantarjian H, Pasquini R, Hamerschlak N, Rousselot P, Holowiecki J, Jootar S, et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial. Blood. 2007;109:5143–5150
  19. Kantarjian HM, Druker BJ, Guilhot F, Cortes J, O'Brien SG, Krahnke T, et al. Imatinib dose escalation is effective in patients with chronic myeloid leukemia in chronic phase (CML-CP). Blood. 2007;110:317a
  20. Kantarjian HM, Larson RA, Guilhot F, O'Brien SG, Mone M, Rudoltz M, et al. Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase. Cancer. 2009;115:551–560
  21. Kantarjian H, Schiffer C, Jones D, Cortes J. Monitoring the response and course of chronic myeloid leukemia in the modern era of BCR-ABL tyrosine kinase inhibitors: practical advice on the use and interpretation of monitoring methods. Blood. 2008;111:1774–1780
  22. Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006;108:28–37
  23. National Comprehensive Cancer Network. NCCN: Clinical practice guidelines in oncology (Chronic myelogenous leukemia). Jenkintown, PA: 2006 National Comprehensive Cancer Network, Inc; 2009;Version 2

 CONFLICT OF INTEREST STATEMENT: Dr Hughes has no conflicts of interest to disclose. Dr Hochhaus has received research support and honoraria for presentations and advisory boards from Novartis Pharmaceuticals Corp.

 Editorial support was provided by Daniel Hutta (Health Interactions) on behalf of Novartis Oncology. A.H. was supported by the German José-Carreras Foundation (DJCLS H 03/01). T.H. is a Practitioner Fellow of the National Health and Medical Council of Australia.

PII: S0037-1963(09)00019-5

doi: 10.1053/j.seminhematol.2009.01.008

Seminars in Hematology
Volume 46 , Pages S11-S15 , April 2009

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