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Chronic Myeloproliferative Neoplasias

First-line imatinib mesylate in patients with newly diagnosed accelerated phase-chronic myeloid leukemia

Abstract

Imatinib mesylate is the sole BCR–ABL tyrosine kinase inhibitor approved as first-line treatment of accelerated-phase (AP) chronic myeloid leukemia (CML). Indication was based on the STI571 0109 study, in which imatinib favorably compared to historical treatments in patients failing prior therapies. The relevance of these results to currently newly diagnosed AP-CML patients remains unknown. We evaluated the benefit of imatinib in 42 newly diagnosed AP-CML patients. In all, 16 patients had hematological acceleration without chromosomal abnormalities in addition to the Philadelphia chromosome (ACAs; HEM-AP), 16 solely had ACAs (ACA-AP) and 10 had hematological acceleration plus ACAs (HEM-AP+ACA). Major cytogenetic responses were achieved in 93.7% of HEM-AP patients, 75% of patients with ACA-AP (P=NS) and 40% of patients with HEM-AP+ACA (P=0.0053). The 24-month failure-free survival rate was 87.5% in HEM-AP patients, 43.8% in ACA-AP patients and 15% in HEM-AP+ACA patients (P=0.022). The 24-month estimate of progression-free survival was 100% in HEM-AP patients, 92.8% in ACA-AP patients and 58.3% in HEM-AP+ACA patients (P=0.0052). In conclusion, frontline imatinib allows favorable outcomes in HEM-AP and ACA-AP patients but appears insufficient for patients with HEM-AP+ACA. Broader-target and/or more potent BCR–ABL tyrosine kinase inhibitors alone or in combination may be considered in this setting.

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References

  1. Sokal JE, Gomez GA, Baccarani M, Tura S, Clarkson BD, Cervantes F et al. Prognostic significance of additional chromosomal abnormalities at diagnosis of Philadelphia chromosome-positive chronic granulocytic leukemia. Blood 1988; 72: 294–298.

    CAS  PubMed  Google Scholar 

  2. Redaelli A, Bell C, Casagrande J, Stephens J, Botteman M, Laskin B et al. Clinical and epidemiologic burden of chronic myelogenous leukemia. Expert Rev Anticancer Ther 2004; 4: 85–96.

    Article  Google Scholar 

  3. Faderl S, Talpaz M, Estrov Z, O’Brien S, Kurzrock R, Kantarjian HM . The biology of chronic myeloid leukemia. New Engl J Med 1999; 341: 164–172.

    Article  CAS  Google Scholar 

  4. Talpaz M, Silver RT, Druker BJ, Goldman JM, Gambacorti-Passerini C, Guilhot F et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood 2002; 99: 1928–1937.

    Article  CAS  Google Scholar 

  5. Kantarjian H, Talpaz M, O’Brien S, Giles F, Faderl S, Vertovsek S et al. Survival benefit with imatinib mesylate therapy in patients with accelerated-phase chronic myelogenous leukemia-comparison with historic experience. Cancer 2005; 103: 2099–2108.

    Article  CAS  Google Scholar 

  6. Silver RT, Cortes J, Waltzman R, Mone M, Kantarjian H . Sustained durability of responses and improved progression-free and overall survival with imatinib treatment for accelerated phase and blast crisis chronic myeloid leukaemia: long-term follow-up of the STI571 0102 and 0109 trials. Haematologica 2009; 94: 743–744.

    Article  Google Scholar 

  7. Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations of an expert panel on behalf of the European LeukemiaNet. Blood 2006; 108: 1809–1820.

    Article  CAS  Google Scholar 

  8. Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009; 27: 6041–6051.

    Article  CAS  Google Scholar 

  9. Kantarjian HM, Dixon D, Keating MJ, Talpaz M, Walters RS, McCredie KB et al. Characteristics of accelerated disease in chronic myelogenous leukemia. Cancer 1988; 61: 1441–1446.

    Article  CAS  Google Scholar 

  10. Cortes J, Talpaz M, O’Brien S, Faderl S, Garcia-Manero G, Ferrajoli A et al. Staging of chronic myeloid leukemia in the imatinib era. Cancer 2006; 106: 1306–1315.

    Article  CAS  Google Scholar 

  11. Shaffer LG, Slovac ML, Campbell LJ (eds). ISCN 2009: An International System for Human Cytogenetic Nomenclature. Karge AG: Basel, Switzerland, 2009.

    Google Scholar 

  12. Kantarjian HM, O’Brien S, Cortes JE, Smith TL, Rios MB, Shan J et al. Treatment of Philadelphia chromosome-positive accelerated-phase chronic myelogenous leukemia with imatinib mesylate. Clin Cancer Res 2002; 8: 2167–2176.

    CAS  PubMed  Google Scholar 

  13. Palandri F, Castagnetti F, Alimena G, Testoni N, Breccia M, Luatti S et al. The long-term durability of cytogenetic responses in patients with accelerated phase chronic myeloid leukemia treated with imatinib 600 mg: the GIMEMA CML Working Party experience after 7-year follow-up. Haematologica 2008; 94: 205–212.

    Article  Google Scholar 

  14. Hochhaus H, Druker B, Sawyers C, Guilhot F, Schiffer CA, Cortes J et al. Favorable long-term follow-up results over 6 years for response, survival and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-α treatment. Blood 2008; 111: 1039–1043.

    Article  CAS  Google Scholar 

  15. 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.

    Article  CAS  Google Scholar 

  16. Fabarius A, Leitner A, Hochhaus A, Müller MC, Hanfstein B, Haferlach C et al. Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV. Blood 2011; 118: 6760–6768.

    Article  CAS  Google Scholar 

  17. O’Dwyer ME, Mauro MJ, Kurilik G, Mori M, Balleisen S, Olson S et al. The impact of clonal evolution on the response to imatinib mesylate (STI571) in accelerated phase CML. Blood 2002; 100: 1628–1633.

    Article  Google Scholar 

  18. Cortes JE, Talpaz M, Giles F, O’Brien S, Rios MB, Shan J et al. Prognostic significance of clonal cytogenetic evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy. Blood 2003; 101: 3794–3800.

    Article  CAS  Google Scholar 

  19. Apperley JF, Cortes JE, Kim D-W, Roy L, Roboz GJ, Rosti G et al. Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START A trial. J Clin Oncol 2009; 27: 3472–3479.

    Article  CAS  Google Scholar 

  20. Le Coutre P, Ottmann OG, Giles F, Kim D-W, Cortes J, Gattermann N et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or –intolerant accelerated-phase chronic myelogenous leukemia. Blood 2008; 111: 1834–1839.

    Article  CAS  Google Scholar 

  21. Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. New Engl J Med 2010; 362: 2260–2270.

    Article  CAS  Google Scholar 

  22. Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C et al. Nilotinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. New Engl J Med 2010; 362: 2251–2259.

    Article  CAS  Google Scholar 

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Acknowledgements

We wish to thank Dr Joelle Guilhot, Center d’Investigation Clinique, CHU Poitiers, France for helpful advice for statistical analysis. We thank clinical research associates for assistance with data collection: Mrs Fabienne Treilhou, Service des Maladies du Sang, Hôpital Saint-Louis, Paris, France; Mrs Marie-Pierre Fort, Service d’Oncologie Médicale, Institut Bergonié, Bordeaux, France; Mrs Madeleine Etienne, Service d’Hématologie Clinique, Hôpital Edouard Herriot, Lyon, France; Mrs Nadine Cadoux, Service d’Hématologie, CH de la region Annécienne, Pringy, France; and Mr Francis Daniel, Service d’Hématologie, Hôpital Purpan, Toulouse, France. The contribution of biologists from hematology and cytogenetics laboratories of participating centers, especially Dr Odile Maarek, Laboratoire Central d’Hématologie, Hôpital Saint-Louis, Paris, France, is gratefully acknowledged.

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Rea, D., Etienne, G., Nicolini, F. et al. First-line imatinib mesylate in patients with newly diagnosed accelerated phase-chronic myeloid leukemia. Leukemia 26, 2254–2259 (2012). https://doi.org/10.1038/leu.2012.92

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