Andreas Hochhaus1, Richard A Larson1, François Guilhot1, Jerald P Radich1, Susan Branford1, Timothy P Hughes1, Michele Baccarani1, Michael W Deininger1, Francisco Cervantes1, Satoko Fujihara1, Christine-Elke Ortmann1, Hans D Menssen1, Hagop Kantarjian1, Stephen G O'Brien1, Brian J Druker1. 1. From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).
Abstract
BACKGROUND:Imatinib, a selective BCR-ABL1 kinase inhibitor, improved the prognosis for patients with chronic myeloid leukemia (CML). We conducted efficacy and safety analyses on the basis of more than 10 years of follow-up in patients with CML who were treated with imatinib as initial therapy. METHODS: In this open-label, multicenter trial with crossover design, we randomly assigned patients with newly diagnosed CML in the chronic phase to receive eitherimatinib or interferon alfa plus cytarabine. Long-term analyses included overall survival, response to treatment, and serious adverse events. RESULTS: The median follow-up was 10.9 years. Given the high rate of crossover among patients who had been randomly assigned to receive interferon alfa plus cytarabine (65.6%) and the short duration of therapy before crossover in these patients (median, 0.8 years), the current analyses focused on patients who had been randomly assigned to receive imatinib. Among the patients in the imatinib group, the estimated overall survival rate at 10 years was 83.3%. Approximately half the patients (48.3%) who had been randomly assigned to imatinib completed study treatment with imatinib, and 82.8% had a complete cytogenetic response. Serious adverse events that were considered by the investigators to be related to imatinib were uncommon and most frequently occurred during the first year of treatment. CONCLUSIONS: Almost 11 years of follow-up showed that the efficacy of imatinib persisted over time and that long-term administration of imatinib was not associated with unacceptable cumulative or late toxic effects. (Funded by Novartis Pharmaceuticals; IRIS ClinicalTrials.gov numbers, NCT00006343 and NCT00333840 .).
RCT Entities:
BACKGROUND:Imatinib, a selective BCR-ABL1 kinase inhibitor, improved the prognosis for patients with chronic myeloid leukemia (CML). We conducted efficacy and safety analyses on the basis of more than 10 years of follow-up in patients with CML who were treated with imatinib as initial therapy. METHODS: In this open-label, multicenter trial with crossover design, we randomly assigned patients with newly diagnosed CML in the chronic phase to receive either imatinib or interferon alfa plus cytarabine. Long-term analyses included overall survival, response to treatment, and serious adverse events. RESULTS: The median follow-up was 10.9 years. Given the high rate of crossover among patients who had been randomly assigned to receive interferon alfa plus cytarabine (65.6%) and the short duration of therapy before crossover in these patients (median, 0.8 years), the current analyses focused on patients who had been randomly assigned to receive imatinib. Among the patients in the imatinib group, the estimated overall survival rate at 10 years was 83.3%. Approximately half the patients (48.3%) who had been randomly assigned to imatinib completed study treatment with imatinib, and 82.8% had a complete cytogenetic response. Serious adverse events that were considered by the investigators to be related to imatinib were uncommon and most frequently occurred during the first year of treatment. CONCLUSIONS: Almost 11 years of follow-up showed that the efficacy of imatinib persisted over time and that long-term administration of imatinib was not associated with unacceptable cumulative or late toxic effects. (Funded by Novartis Pharmaceuticals; IRIS ClinicalTrials.gov numbers, NCT00006343 and NCT00333840 .).
Authors: Carlo Gambacorti-Passerini; Laura Antolini; François-Xavier Mahon; Francois Guilhot; Michael Deininger; Carmen Fava; Arnon Nagler; Chiara Maria Della Casa; Enrica Morra; Elisabetta Abruzzese; Anna D'Emilio; Fabio Stagno; Philipp le Coutre; Rafael Hurtado-Monroy; Valeria Santini; Bruno Martino; Fabrizio Pane; Andrea Piccin; Pilar Giraldo; Sarit Assouline; Muheez A Durosinmi; Onno Leeksma; Enrico Maria Pogliani; Miriam Puttini; Eunjung Jang; Josy Reiffers; Maria Grazia Valsecchi; Dong-Wook Kim Journal: J Natl Cancer Inst Date: 2011-03-21 Impact factor: 13.506
Authors: Elias Jabbour; Hagop M Kantarjian; Giuseppe Saglio; Juan Luis Steegmann; Neil P Shah; Concepción Boqué; Charles Chuah; Carolina Pavlovsky; Jirí Mayer; Jorge Cortes; Michele Baccarani; Dong-Wook Kim; M Brigid Bradley-Garelik; Hesham Mohamed; Mark Wildgust; Andreas Hochhaus Journal: Blood Date: 2013-12-05 Impact factor: 22.113
Authors: Rüdiger Hehlmann; Ute Berger; Markus Pfirrmann; Hermann Heimpel; Andreas Hochhaus; Joerg Hasford; Hans-Jochem Kolb; Tanja Lahaye; Ole Maywald; Andreas Reiter; Dieter K Hossfeld; Christoph Huber; Helmut Löffler; Hans Pralle; Wolfgang Queisser; Andreas Tobler; Christoph Nerl; Max Solenthaler; Mariele E Goebeler; Martin Griesshammer; Thomas Fischer; Stephan Kremers; Hartmut Eimermacher; Michael Pfreundschuh; Wolf-Dietrich Hirschmann; Klaus Lechner; Barbara Wassmann; Christiane Falge; Hartmut H Kirchner; Alois Gratwohl Journal: Blood Date: 2007-02-22 Impact factor: 22.113
Authors: Susanne Saussele; Marie-Paloma Krauss; Rüdiger Hehlmann; Michael Lauseker; Ulrike Proetel; Lida Kalmanti; Benjamin Hanfstein; Alice Fabarius; Doris Kraemer; Wolfgang E Berdel; Martin Bentz; Peter Staib; Maike de Wit; Martin Wernli; Florian Zettl; Holger F Hebart; Markus Hahn; Jochen Heymanns; Ingo Schmidt-Wolf; Norbert Schmitz; Michael J Eckart; Winfried Gassmann; Andrea Bartholomäus; Antonio Pezzutto; Elisabeth Oppliger Leibundgut; Dominik Heim; Stefan W Krause; Andreas Burchert; Wolf-Karsten Hofmann; Joerg Hasford; Andreas Hochhaus; Markus Pfirrmann; Martin C Müller Journal: Blood Date: 2015-04-27 Impact factor: 22.113
Authors: A Hochhaus; S G O'Brien; F Guilhot; B J Druker; S Branford; L Foroni; J M Goldman; M C Müller; J P Radich; M Rudoltz; M Mone; I Gathmann; T P Hughes; R A Larson Journal: Leukemia Date: 2009-03-12 Impact factor: 11.528
Authors: Rüdiger Hehlmann; Martin C Müller; Michael Lauseker; Benjamin Hanfstein; Alice Fabarius; Annette Schreiber; Ulrike Proetel; Nadine Pletsch; Markus Pfirrmann; Claudia Haferlach; Susanne Schnittger; Hermann Einsele; Jolanta Dengler; Christiane Falge; Lothar Kanz; Andreas Neubauer; Michael Kneba; Frank Stegelmann; Michael Pfreundschuh; Cornelius F Waller; Karsten Spiekermann; Gabriela M Baerlocher; Gerhard Ehninger; Dominik Heim; Hermann Heimpel; Christoph Nerl; Stefan W Krause; Dieter K Hossfeld; Hans-Jochem Kolb; Joerg Hasford; Susanne Saußele; Andreas Hochhaus Journal: J Clin Oncol Date: 2013-12-02 Impact factor: 44.544
Authors: J E Cortes; D-W Kim; J Pinilla-Ibarz; P le Coutre; R Paquette; C Chuah; F E Nicolini; J F Apperley; H J Khoury; M Talpaz; J DiPersio; D J DeAngelo; E Abruzzese; D Rea; M Baccarani; M C Müller; C Gambacorti-Passerini; S Wong; S Lustgarten; V M Rivera; T Clackson; C D Turner; F G Haluska; F Guilhot; M W Deininger; A Hochhaus; T Hughes; J M Goldman; N P Shah; H Kantarjian Journal: N Engl J Med Date: 2013-11-01 Impact factor: 91.245
Authors: Michele Baccarani; Michael W Deininger; Gianantonio Rosti; Andreas Hochhaus; Simona Soverini; Jane F Apperley; Francisco Cervantes; Richard E Clark; Jorge E Cortes; François Guilhot; Henrik Hjorth-Hansen; Timothy P Hughes; Hagop M Kantarjian; Dong-Wook Kim; Richard A Larson; Jeffrey H Lipton; François-Xavier Mahon; Giovanni Martinelli; Jiri Mayer; Martin C Müller; Dietger Niederwieser; Fabrizio Pane; Jerald P Radich; Philippe Rousselot; Giuseppe Saglio; Susanne Saußele; Charles Schiffer; Richard Silver; Bengt Simonsson; Juan-Luis Steegmann; John M Goldman; Rüdiger Hehlmann Journal: Blood Date: 2013-06-26 Impact factor: 22.113
Authors: Heather A Himburg; Martina Roos; Tiancheng Fang; Yurun Zhang; Christina M Termini; Lauren Schlussel; Mindy Kim; Amara Pang; Jenny Kan; Liman Zhao; Hyung Suh; Joshua P Sasine; Gopal Sapparapu; Peter M Bowers; Gary Schiller; John P Chute Journal: J Clin Invest Date: 2020-01-02 Impact factor: 14.808
Authors: Hein Than; Anthony D Pomicter; Dongqing Yan; Larry P Beaver; Anna M Eiring; William L Heaton; Anna Senina; Phillip M Clair; Sharon Shacham; Clinton C Mason; Thomas O' Hare; Michael W Deininger Journal: Leukemia Date: 2020-01-24 Impact factor: 11.528
Authors: Christopher A Eide; Matthew S Zabriskie; Samantha L Savage Stevens; Orlando Antelope; Nadeem A Vellore; Hein Than; Anna Reister Schultz; Phillip Clair; Amber D Bowler; Anthony D Pomicter; Dongqing Yan; Anna V Senina; Wang Qiang; Todd W Kelley; Philippe Szankasi; Michael C Heinrich; Jeffrey W Tyner; Delphine Rea; Jean-Michel Cayuela; Dong-Wook Kim; Cristina E Tognon; Thomas O'Hare; Brian J Druker; Michael W Deininger Journal: Cancer Cell Date: 2019-09-19 Impact factor: 31.743