Multicenter Independent Assessment of Outcomes in Chronic Myeloid Leukemia Patients Treated With Imatinib
Carlo Gambacorti-Passerini,Laura Antolini,Franois Xavier Mahon,François Guilhot,Michael W. 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,P Giraldo,Sarit Assouline,Muheez A. Durosinmi,O. C. Leeksma,Enrico Pogliani,Miriam Puttini,Eun-Jung Jang,Josy Reiffers,Maria Grazia Valsecchi,Dong-Wook Kim +27 more
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TLDR
In this study, CML-related deaths were uncommon in CML patients who were in CCyR 2 years after starting imatinib, and survival was not statistically significantly different from that of the general population.Abstract:
BACKGROUND Imatinib slows development of chronic myeloid leukemia (CML). However, available information on morbidity and mortality is largely based on sponsored trials, whereas independent long-term field studies are lacking. PATIENTS AND METHODS Consecutive CML patients who started imatinib treatment before 2005 and who were in complete cytogenetic remission (CCyR) after 2 years (± 3 months) were eligible for enrollment in the independent multicenter Imatinib Long-Term (Side) Effects (ILTE) study. Incidence of the first serious and nonserious adverse events and loss of CCyR were estimated according to the Kaplan-Meier method and compared with the standard log-rank test. Attainment of negative Philadelphia chromosome hematopoiesis was assessed with cytogenetics and quantitative polymerase chain reaction. Cumulative incidence of death related or unrelated to CML progression was estimated, accounting for competing risks, according to the Kalbleisch-Prentice method. Standardized incidence ratios were calculated based on population rates specific for sex and age classes. Confidence intervals were calculated by the exact method based on the χ(2) distribution. All statistical tests were two-sided. RESULTS A total of 832 patients who were treated for a median of 5.8 years were enrolled. There were 139 recorded serious adverse events, of which 19.4% were imatinib-related. A total of 830 nonserious adverse events were observed in 53% of patients; 560 (68%) were imatinib-related. The most frequent were muscle cramps, asthenia, edema, skin fragility, diarrhea, tendon, or ligament lesions. Nineteen patients (2.3%) discontinued imatinib because of drug-related toxic effects. Forty-five patients lost CCyR, at a rate of 1.4 per 100 person-years. Durable (>1 year) negative Philadelphia chromosome hematopoiesis was attained by 179 patients. Twenty deaths were observed, with a 4.8% mortality incidence rate (standardized incidence ratio = 0.7; 95% confidence interval = 0.40 to 1.10, P = .08), with only six (30%) associated with CML progression. CONCLUSIONS In this study, CML-related deaths were uncommon in CML patients who were in CCyR 2 years after starting imatinib, and survival was not statistically significantly different from that of the general population.read more
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Journal ArticleDOI
Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia
Andreas Hochhaus,Richard A. Larson,François Guilhot,Jerald P. Radich,Susan Branford,Timothy P. Hughes,Michele Baccarani,Michael W. Deininger,Francisco Cervantes,Satoko Fujihara,Christine Elke Ortmann,Hans D. Menssen,Hagop M. Kantarjian,Stephen G. O'Brien,Brian J. Druker +14 more
TL;DR: 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.
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Evolutionary dynamics of cancer in response to targeted combination therapy
Ivana Bozic,Johannes G. Reiter,Benjamin L. Allen,Benjamin L. Allen,Tibor Antal,Krishnendu Chatterjee,Preya Shah,Yo Sup Moon,Amin Yaqubie,Nicole Kelly,Dung T. Le,Evan J. Lipson,Paul B. Chapman,Luis A. Diaz,Bert Vogelstein,Martin A. Nowak +15 more
TL;DR: It is found that dual therapy results in long-term disease control for most patients, if there are no single mutations that cause cross-resistance to both drugs; in patients with large disease burden, triple therapy is needed.
Journal ArticleDOI
The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts
Camille N. Abboud,Ellin Berman,Adam D. Cohen,Jorge E. Cortes,Daniel J. DeAngelo,Michael W. Deininger,Steven M. Devine,Brian J. Druker,Amir T. Fathi,Elias Jabbour,Madan Jagasia,Hagop M. Kantarjian,Jean Khoury,Pierre Laneuville,Richard A. Larson,Jeffrey H. Lipton,Joseph O. Moore,Tariq I. Mughal,Susan O'Brien,Javier Pinilla-Ibarz,Alfonso Quintás-Cardama,Jerald P. Radich,Vishnu Reddy,Charles A. Schiffer,Neil P. Shah,Paul J. Shami,Richard T. Silver,David S. Snyder,Richard Stone,Moshe Talpaz,Ayalew Tefferi,Richard A. Van Etten,Meir Wetzler,Elisabetta Abruzzese,Jane F. Apperley,Massimo Breccia,Jenny Byrne,Francisco Cervantes,Ekaterina Chelysheva,Richard E. Clark,Hugues de Lavallade,Iryna Dyagil,Carlo Gambacorti-Passerini,John M. Goldman,Ibrahim C. Haznedaroglu,Henrik Hjorth-Hansen,Tessa L. Holyoake,Brian J. P. Huntly,Philipp le Coutre,Elza Lomaia,Francois-Xavier Mahon,David Marin-Costa,Giovanni Martinelli,Jiri Mayer,Dragana Milojkovic,Eduardo Olavarria,Kimmo Porkka,Johan Richter,Philippe Rousselot,Giuseppe Saglio,Güray Saydam,Jesper Stentoft,Anna G. Turkina,Paolo Vigneri,Andrey Zaritskey,Alvaro Aguayo,Manuel Ayala,Israel Bendit,Raquel Bengió,Carlos Best,Eduardo Bullorsky,Eduardo Cervera,Carmino DeSouza,Ernesto Fanilla,David Gómez-Almaguer,Nelson Hamerschlak,José A. López,Alicia Magarinos,Luis Meillon,Jorge Milone,Beatriz Moiraghi,Ricardo Pasquini,Carolina Pavlovsky,Guillermo J. Ruiz-Argüelles,Nelson Spector,Christopher Arthur,Peter Browett,Andrew Grigg,Jianda Hu,Xiao-Jun Huang,Timothy P. Hughes,Qian Jiang,Saengsuree Jootar,Dong-Wook Kim,Hemant Malhotra,Pankaj Malhotra,Itaru Matsumura,Junia V. Melo,Kazunori Ohnishi,Ryuzo Ohno,Tapan Saikia,Anthony P. Schwarer,Naoto Takahashi,Constantine S. Tam,Tetsuzo Tauchi,Kensuke Usuki,Jianxiang Wang,Fawzi Abdel-Rahman,Mahmoud Aljurf,Ali Bazarbachi,Dina Ben Yehuda,Naeem Chaudhri,Muheez A. Durosinmi,Hossam Kamel,Vernon J. Louw,Bassam Francis Matti,Arnon Nagler,Pia Raanani,Ziad Salem +118 more
TL;DR: There is a need to (1) lower the prices of cancer drugs to allow more patients to afford them and (2) maintain sound long-term health care policies.
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Cost Sharing and Adherence to Tyrosine Kinase Inhibitors for Patients With Chronic Myeloid Leukemia
TL;DR: A critical need to reduce patient costs for TKI adherence and discontinuation is suggested, as patients with higher copayments are more likely to discontinue or be nonadherent to TKIs.
Journal ArticleDOI
Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML).
Benjamin Hanfstein,Martin C. Müller,Rüdiger Hehlmann,Philipp Erben,Michael Lauseker,Alice Fabarius,Susanne Schnittger,Claudia Haferlach,Gudrun Göhring,Ulrike Proetel,Hans-Jochem Kolb,Stefan W. Krause,Wolf-K. Hofmann,J. Schubert,H. Einsele,Jolanta Dengler,Mathias Hänel,C. Falge,Lothar Kanz,Andreas Neubauer,Michael Kneba,Frank Stegelmann,Michael Pfreundschuh,Cornelius F. Waller,Susan Branford,Susan Branford,Timothy P. Hughes,Karsten Spiekermann,Gabriela M. Baerlocher,Markus Pfirrmann,Joerg Hasford,Susanne Saußele,Andreas Hochhaus +32 more
TL;DR: Treatment optimization is recommended for pts missing these landmarks and early prediction of prognosis on imatinib is desirable to assure favorable survival or otherwise consider the use of a second-generation tyrosine kinase inhibitor (TKI).
References
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Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia
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TL;DR: Imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML and was better tolerated than combination therapy.
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Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
Brian J. Druker,François Guilhot,Stephen G. O'Brien,Insa Gathmann,Hagop M. Kantarjian,Norbert Gattermann,Michael W. Deininger,Richard T. Silver,John M. Goldman,Richard Stone,Francisco Cervantes,Andreas Hochhaus,Bayard L. Powell,Janice Gabrilove,Philippe Rousselot,Josy Reiffers,Jan J. Cornelissen,Timothy P. Hughes,Hermine Agis,Thea Kolsen Fischer,Gregor Verhoef,John D. Shepherd,Giuseppe Saglio,Alois Gratwohl,Johan Lanng Nielsen,Jerald P. Radich,Bengt Simonsson,Kerry Taylor,Michele Baccarani,Charlene So,Laurie Letvak,Richard A. Larson +31 more
TL;DR: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients.
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Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia
Hagop M. Kantarjian,Charles L. Sawyers,Andreas Hochhaus,François Guilhot,Charles A. Schiffer,Carlo Gambacorti-Passerini,Dietger Niederwieser,Debra Resta,Renaud Capdeville,Ulrike Zoellner,Moshe Talpaz,Brian J. Druker +11 more
TL;DR: Imatinib induced high rates of cytogenetic and hematologic responses in patients with chronic-phase CML in whom previous interferon therapy had failed, and CML had not progressed to the accelerated or blast phases after a median follow-up of 18 months.
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