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Chronic Myeloproliferative Neoplasias

Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia

A Corrigendum to this article was published on 12 May 2010

Abstract

Imatinib mesylate is considered standard of care for first-line treatment of chronic phase chronic myeloid leukemia (CML-CP). In the phase III, randomized, open-label International Randomized Study of Interferon vs STI571 (IRIS) trial, previously untreated CML-CP patients were randomized to imatinib (n=553) or interferon-α (IFN) plus cytarabine (n=553). This 6-year update focuses on patients randomized to receive imatinib as first-line therapy for newly diagnosed CML-CP. During the sixth year of study treatment, there were no reports of disease progression to accelerated phase (AP) or blast crisis (BC). The toxicity profile was unchanged. The cumulative best complete cytogenetic response (CCyR) rate was 82%; 63% of all patients randomized to receive imatinib and still on study treatment showed CCyR at last assessment. The estimated event-free survival at 6 years was 83%, and the estimated rate of freedom from progression to AP and BC was 93%. The estimated overall survival was 88%––or 95% when only CML-related deaths were considered. This 6-year update of IRIS underscores the efficacy and safety of imatinib as first-line therapy for patients with CML.

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References

  1. Goldman JM, Melo JV . Chronic myeloid leukemia––advances in biology and new approaches to treatment. N Engl J Med 2003; 349: 1451–1464.

    CAS  Article  PubMed  Google Scholar 

  2. Ren R . Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nat Rev Cancer 2005; 5: 172–183.

    CAS  Article  PubMed  Google Scholar 

  3. Steelman LS, Pohnert SC, Shelton JG, Franklin RA, Bertrand FE, McCubrey JA . JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BCR-ABL in cell cycle progression and leukemogenesis. Leukemia 2004; 18: 189–218.

    CAS  Article  PubMed  Google Scholar 

  4. Van Etten RA . Mechanisms of transformation by the BCR-ABL oncogene: new perspectives in the post-imatinib era. Leuk Res 2004; 28 Suppl 1: S21–S28.

    CAS  Article  PubMed  Google Scholar 

  5. McGahon A, Bissonnette R, Schmitt M, Cotter KM, Green DR, Cotter TG . BCR-ABL maintains resistance of chronic myelogenous leukemia cells to apoptotic cell death. Blood 1994; 83: 1179–1187.

    CAS  PubMed  Google Scholar 

  6. Sirard C, Laneuville P, Dick JE . Expression of bcr-abl abrogates factor-dependent growth of human hematopoietic M07E cells by an autocrine mechanism. Blood 1994; 83: 1575–1585.

    CAS  PubMed  Google Scholar 

  7. Schindler T, Bornmann W, Pellicena P, Miller WT, Clarkson B, Kuriyan J . Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science 2000; 289: 1938–1942.

    CAS  Article  PubMed  Google Scholar 

  8. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 1996; 2: 561–566.

    CAS  Article  PubMed  Google Scholar 

  9. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001; 344: 1031–1037.

    CAS  Article  PubMed  Google Scholar 

  10. 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 

  11. Sawyers CL, Hochhaus A, Feldman E, Goldman JM, Miller CB, Ottmann OG et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood 2002; 99: 3530–3539.

    CAS  Article  PubMed  Google Scholar 

  12. 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.

    CAS  Article  PubMed  Google Scholar 

  13. Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002; 346: 645–652.

    CAS  Article  PubMed  Google Scholar 

  14. Kantarjian HM, Cortes J, O’Brien S, Giles FJ, Albitar M, Rios MB et al. Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase. Blood 2002; 99: 3547–3553.

    CAS  Article  PubMed  Google Scholar 

  15. Kantarjian HM, O’Brien S, Cortes JE, Giralt SA, Rios MB, Shan J et al. Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood 2002; 100: 1590–1595.

    CAS  PubMed  Google Scholar 

  16. 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.

    Article  PubMed  Google Scholar 

  17. 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.

    CAS  Article  PubMed  Google Scholar 

  18. 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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Kerkelä R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 2006; 12: 908–916.

    Article  PubMed  Google Scholar 

  20. Branford S, Seymour JF, Grigg A, Arthur C, Rudzki Z, Lynch K et al. BCR-ABL messenger RNA levels continue to decline in patients with chronic phase chronic myeloid leukemia treated with imatinib for more than 5 years and approximately half of all first-line treated patients have stable undetectable BCR-ABL using strict sensitivity criteria. Clin Cancer Res 2007; 13: 7080–7085.

    CAS  Article  PubMed  Google Scholar 

  21. Petzer AL, Eaves CJ, Lansdorp PM, Ponchio L, Barnett MJ, Eaves AC . Characterization of primitive subpopulations of normal and leukemic cells present in the blood of patients with newly diagnosed as well as established chronic myeloid leukemia. Blood 1996; 88: 2162–2171.

    CAS  PubMed  Google Scholar 

  22. Deininger MW, O’Brien SG, Ford JM, Druker BJ . Practical management of patients with chronic myeloid leukemia receiving imatinib. J Clin Oncol 2003; 21: 1637–1647.

    CAS  Article  PubMed  Google Scholar 

  23. Verweij J, Casali PG, Kotasek D, Le Cesne A, Reichard P, Judson IR et al. Imatinib does not induce cardiac left ventricular failure in gastrointestinal stromal tumours patients: analysis of EORTC-ISG-AGITG study 62005. Eur J Cancer 2007; 43: 974–978.

    CAS  Article  PubMed  Google Scholar 

  24. Atallah E, Durand JB, Kantarjian H, Cortes J . Congestive heart failure is a rare event in patients receiving imatinib therapy. Blood 2007; 110: 1233–1237.

    CAS  Article  PubMed  Google Scholar 

  25. Hatfield A, Owen S, Pilot PR . In reply to ‘Cardiotoxicity of the cancer therapeutic agent imatinib mesylate’. Nat Med 2007; 13: 13 author reply 15–16.

    CAS  Article  PubMed  Google Scholar 

  26. Gambacorti-Passerini C, Tornaghi L, Franceschino A, Piazza R, Corneo G, Pogliani E . In reply to ‘Cardiotoxicity of the cancer therapeutic agent imatinib mesylate’. Nat Med 2007; 13: 13, 4; author reply 15–16.

    Article  PubMed  Google Scholar 

  27. Rosti G, Martinelli G, Baccarani M . In reply to ‘Cardiotoxicity of the cancer therapeutic agent imatinib mesylate’. Nat Med 2007; 13: 15, author reply 15–16.

    CAS  Article  PubMed  Google Scholar 

  28. American Cancer Society. Cancer Facts and Figures 2007. American Cancer Society: Atlanta, 2007.

  29. National Comprehensive Cancer Network. NCCN: Clinical practice guidelines in oncology. Chronic Myelogenous Leukemia. Version 2. November 26, 2008, Accessed online at www.nccn.org.

  30. 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.

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgements

This research study was supported by Novartis (for all investigators); AH received support from the German José-Carreras Foundation (DJCLS H 03/01)

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Correspondence to A Hochhaus.

Appendix

Appendix

The following investigators participated in IRIS: Australia––Hanson Institute Centre for Cancer, Adelaide: T Hughes; Mater Hospital, Brisbane: K Taylor; Royal Brisbane Hospital, Herston: S Durant; Monash Medical Center, Melbourne: A Schwarer; Sir Charles Gardner Hospital, Perth: D Joske; Australia Leukemia and Lymphoma Group, Melbourne: J Seymour; Royal Melbourne Hospital, Parkville: A Grigg; St Vincent's Hospital, Darlinghurst: D Ma; Royal North Shore Hospital, St Leonards: C Arthur; Westmead Hospital: K Bradstock; Royal Prince Alfred Hospital, Sydney: D Joshua. Austria––Universitätsklinik für Innere Medizin I, Vienna: H Agis. Belgium––University Hospital Gasthuisberg, Leuven: G Verhoef; AZ Sint-Jan, Brugge: A Louwagie; Institut Jules Bordet, Brussels: P Martiat; Cliniques Universitaries, Yvoir: A Bosly. Canada––Vancouver Hospital: J Shepherd; McGill University, Montreal: C Shistok; Princess Margaret Hospital, Toronto: J Lipton; Queen Elizabeth II Health Sciences Center, Halifax: D Forrest; McMaster University Medical Centre, West Hamilton: I Walker; Universite de Montreal, Montreal: D-C Roy; Cancer Care, Winnepeg: M Rubinger; Ottawa Hospital Regional Cancer Centre: I Bence-Bruckler; University of Calgary: D Stewart; London Regional Cancer Centre: M Kovacs; Cross Cancer Center, Edmonton: A-R Turner. Denmark––Aarhus Amtssygehus: J Nielsen; Kobenhavns Amts Sygehus I Gentofte, Hellerup: H Birgens; Danish University of Pharmaceutical Sciences, Copenhagen: O Bjerrum. France––Hôpital Saint Louis, Paris: P Rousselot; Centre Hospitalier Universitaire de Bordeaux, Pessac: J Reiffers; Hôpital Claude Huriez, Lille: T Facon; Hotel Dieu Hospital, Nantes: J-L Harousseau; Henri Mondor Hospital, Creteil: M Tulliez; Centre Hospitalier Universitaire (CHU) Braboi, Vandoueuvre-les Nancy: A Guerci; Institut Paoli-Calmettes, Marseille: D Blaise; Hôpital Civil, Strasbourg: F Maloisel; CHU la Miletrie, Poitiers: M Michallet. Germany––Johannes Gutenberg Universitat, Mainz: T Fischer; Universitaetsmedizin Mannheim: A Hochhaus; University of Regensburg, Regensburg: R Andreesen; Krankenhaus Muenchen-Schwabing, Munich: C Nerl; University Hospital Rostock: M Freund; Heinrich-Heine-Universitaet Duesseldorf: N Gattermann; University Hospital Carl Gustav Carus, Dresden: G Ehninger; University Hospital, Leipzig: D Niederwieser; Johann Wolfgang Goethe University Hospital, Frankfurt: OG Ottmann; University Hospital Rechts der Isar, Munich: C Peschel; University of Heidelberg, Heidelberg: AD Ho; Philipps-Universitaet Marburg: A Neubauer; Humboldt-Universitaet, Berlin: P le Coutre; Robert-Bosch-Hospital, Stuttgart: W Aulitzky. Italy––Azienda Ospedaliera S Luigi Gonzaga, Orbassano: G Saglio; Policlinico S Orsola–Malpighi, Bologna: M Baccarani; University Hospital, Udine: R Fanin; San Orsola Hospital, Bologna: G Rosti; Universita La Sapienza, Rome: F Mandelli; Instituto di Ricovero e Cura a Carattre Scientifico (IRCCS) Policlinico San Matteo, Pavia: M Lazzarino; Niguarda Ca’Granda Hospital, Milan: E Morra; Azienda Osperdaliera e Cliniche Univerditarie San Martino, Largo R Benzi, Genoa: A Carella; University of Pisa, Pisa: M Petrini; Azienda Ospedaliera Bianchi-Malcrino-Morelli, Reggio Calabria: F Nobile; University of Bari, Policlinico, Bari: V Liso; Cardelli Hospital, Naples: F Ferrara; University of Parma, Parma: V Rizzoli; Ospedal Civile, Pescara: G Fiortoni; Institute of Hematology and Medical Oncology Seragnoli, Bologna: G Martinelli. The Netherlands––Erasmus Medical Center, Rotterdam: J Cornelissen; Vrje Universiteit Academic Medical Center, Amsterdam: G Ossenkoppele. New Zealand––University of Auckland, Auckland: P Browett. Norway––Medisinsk Avdeling, Rikshospitalet, Oslo: T Gedde-Dahl; Ullevål Sykehus, Oslo: J-M Tangen; Hvidovre Hospital, Betalende: I Dahl. Spain––Hospital Clinic I Provincial, Barcelona: F Cervantes; Hospital Clinic,Villarroel, Barcelona: J Odrizoala; University of Barcelona: JC Hernandez Boulda; Hospital Universitarui de la Princesa, Madrid: JL Steegmann; Hospital Universitario de Salamanca: C Canizo; San Carlos Clinical Hospital, Madrid: J Diaz; Institut Catala d’Oncologia, Barcelona: A Grenena; Hospital Lluis Alcanyis, Cta Xativa-Silla: M Fernandez. Sweden––Akademiska Sjukhuset, Uppsala: B Simonsson; Karolinska Hospital, Stockholm: L Stenke; Huddinge Sjukhus, Huddinge: C Paul; Medicinkliniken Universitetssjukhuset, Obrebro: M Bjoreman; Regionsjukhuset, Linkoping: C Malm; Sahlgrenska Hospital, Goteborg: H Wadenvik; Endokinsekt/Medklin Universitetssjukhuset, Lund: P-G Nilsson; Universitetssjukhuset Malmo University Hospital, Malmo: I Turesson. Switzerland––University Hospital Basel: A Gratwohl; Kantonsspital, St Gallen: U Hess; University of Bern: M Solenthaler. United Kingdom––Imperial College London: JM Goldman; Department of Haematology, University of Liverpool, Medical School, Liverpool: RE Clark; Cambridge Institute for Medical Research, Cambridge: A Green; Glasgow Royal Infirmary: T Holyoake; Manchester Royal Infirmary: G Lucas; Leeds General Infirmary: G Smith; Queen Elizabeth Hospital, Edgbaston, Birmingham: D Milligan; Derriford Hospital, Plymouth: S Rule; University Hospital of Wales, Cardiff: A Burnett. United States––MD Anderson Cancer Center, Houston: H Kantarjian; Weill–Cornell Medical Center, New York: R Silver; Dana–Farber Cancer Institute, Boston: R Stone; Wake Forest University Baptist Medical Center, Winston-Salem: B Powell; Mount Sinai School of Medicine, New York: J Gabrilove; Walt Disney Memorial Cancer Institute, Orlando: R Moroose; Roswell Park Cancer Center, Buffalo: M Wetzler; Gibbs Cancer Center, Spartanburg: J Bearden; Ohio State University School of Medicine, Columbus: S Cataland; University of New Mexico Health Sciences Center, Albuquerque: I Rabinowitz; University of Maryland Cancer Center, Baltimore: B Meisenberg; Montgomery Cancer Center, Montgomery: K Thompson; State University of New York Upstate Medical Center, Syracuse: S Graziano; University of Alabama at Birmingham: P Emanuel; Hematology and Oncology Inc., Dayton: H Gross; Billings Oncology Associates, Billings: P Cobb; City of Hope National Medical Center, Duarte: R Bhatia; Cancer Center of Kansas Wichita: S Dakhil; Alta Bates Comprehensive Cancer Center, Berkeley: AD Irwin; Cancer Research Center of Hawaii, Honolulu: B Issell; University of Nebraska Medical Center, Omaha: S Pavletic; Columbus Community Clinical Oncology Program: P Kuebler; Michigan State University Hematology/Oncology, Lansing: E Layhe; Brown University School of Medicine, Providence: P Butra; Loyola University Medical Center, Shreveport: J Glass; Duke University Medical Center, Durham: J Moore; University of Vermont, Burlington: B Grant; University of Tennessee, Memphis: H Neill; University of Louisville: R Herzig; Sarah Cannon Cancer Center, Nashville: H Burris; University of Minnesota, Minneapolis: B Petersen; Cleveland Clinic Foundation: M Kalaycio; Fred Hutchinson Cancer Research Center, Seattle: D Stirewalt; University of Utah, Salt Lake City: W Samlowski; Memorial Sloan-Kettering Cancer Center, New York: E Berman; University of North Carolina School of Medicine, Charlotte: S Limentani; Atlanta Cancer Center: T Seay; University of North Carolina School of Medicine, Chapel Hill: T Shea; Indiana Blood and Marrow Institute, Beech Grove: L Akard; San Juan Regional Cancer Center, Farmington: G Smith; University of Massachusetts Memorial Medical Center, Worcester: P Becker; Washington University School of Medicine, St Louis: S Devine; Veterans Affairs Medical Center, Milwaukee: R Hart; Louisiana State University Medical Center, New Orleans: RVeith; Decatur Memorial Hospital, Decatur: J Wade; Rocky Mountain Cancer Centers, Denver: M Brunvad; Oncology-Hematology Group of South Florida, Miami: L Kalman; Memphis Cancer Center, Memphis: D Strickland; Henry Ford Hospital, Detroit: M Shurafa; University of California, San Diego, Medical Center, La Jolla: A Bashey; Western Pennsylvania Cancer Institute, Pittsburgh: R Shadduck; Tulane Cancer Center, New Orleans: H Safah; Southbay Oncology Hematology Partners, Campbell: M Rubenstein; University of Texas Southwest Medical Center, Dallas: R Collins; Cancer Care Associates, Tulsa: A Keller; Robert H Lurie Comprehensive Cancer Center, Chicago: M Tallman; Northern New Jersey Cancer Center, Hackensack: A Pecora; University of Pittsburgh Medical Center, Hillman Cancer Center: M Agha; Texas Oncology, Dallas: H Homes; and New Mexico Oncology Hematology Consultants Albuquerque: R Guidice. Study Management Committee: Oregon Health and Science University, Portland: BJ Druker; University Hospital, Poitiers: F Guilhot; University of Chicago, Chicago: RA Larson; University of Newcastle upon Tyne: S O’Brien. Independent Data Monitoring Board: Rambam Medical Center, Haifa, Israel: J Rowe; Wayne State University, Barbara Ann Karmanos Cancer Institute, Detroit: CA Schiffer; International Drug Development Institute, Brussels: M Buyse. Protocol Working Group: Policlinico San Orsola-Malpighi, Bologna: M Baccarani; Hospital Clinical, Barcelona: F Cervantes; Erasmus Medical Center, Rotterdam: J Cornelissen; Johannes Gutenberg Universitat, Mainz: T Fischer; Universitaetsmedizin Mannheim: A Hochhaus; Hanson Institute Centre for Cancer, Adelaide: T Hughes; Medical University of Vienna: K Lechner; Aarhus Amtsygehus, Aarhus: JL Nielsen; CHU de Bordeaux, Pessac: J Reiffers; Hopital Saint Louis, Paris: P Rousselot; San Luigi Gonzaga Hospital, Turin: G Saglio; Vancouver Hospital: J Shepherd; Akademiska Sjukhuset, Uppsala: B Simonsson; University Hospital, Basel: A Gratwohl; Imperial College, London: JM Goldman; University of Michigan Health System, Ann Arbor: M Talpaz; Mater Misericordiae Public Hospital, Brisbane: K Taylor; and University Hospital Gathuisberg, Leuven: G Verhoef.

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Hochhaus, A., O'Brien, S., Guilhot, F. et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 23, 1054–1061 (2009). https://doi.org/10.1038/leu.2009.38

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Keywords

  • chronic myeloid leukemia
  • chronic phase
  • imatinib

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