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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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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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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DOI: https://doi.org/10.1038/leu.2009.38
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