Journal ArticleDOI
Deep Molecular Response Is Reached by the Majority of Patients Treated With Imatinib, Predicts Survival, and Is Achieved More Quickly by Optimized High-Dose Imatinib: Results From the Randomized CML-Study IV
Rüdiger Hehlmann,Martin C. Müller,Michael Lauseker,Benjamin Hanfstein,Alice Fabarius,Annette Schreiber,Ulrike Proetel,Nadine Pletsch,Markus Pfirrmann,Claudia Haferlach,Susanne Schnittger,H. 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 +31 more
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MR(4.5) is a new molecular predictor of long-term outcome, is reached by a majority of patients treated with imatinib, and is achieved more quickly with optimized high-dose imatin ib, which may provide an improved therapeutic basis for treatment discontinuation in CML.Abstract:
Purpose Deep molecular response (MR 4.5 ) defines a subgroup of patients with chronic myeloid leukemia (CML) who may stay in unmaintained remission after treatment discontinuation. It is unclear how many patients achieve MR 4.5 under different treatment modalities and whether MR 4.5 predicts survival. Patients and Methods Patients from the randomized CML-Study IV were analyzed for confirmed MR 4.5 which was defined as 4.5 log reduction of BCR-ABL on the international scale (IS) and determined by reverse transcriptase polymerase chain reaction in two consecutive analyses. Landmark analyses were performed to assess the impact of MR 4.5 on survival. Results Of 1,551 randomly assigned patients, 1,524 were assessable. After a median observation time of 67.5 months, 5-year overall survival (OS) was 90%, 5-year progression-free-survival was 87.5%, and 8-year OS was 86%. The cumulative incidence of MR 4.5 after 9 years was 70% (median, 4.9 years); confirmed MR 4.5 was 54%. MR 4.5 was reached more quickly with optimized high-doseread 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.
Journal ArticleDOI
European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia
Andreas Hochhaus,Michele Baccarani,Richard T. Silver,Charles A. Schiffer,Jane F. Apperley,Francisco Cervantes,Richard E. Clark,Jorge E. Cortes,Michael W. Deininger,François Guilhot,Henrik Hjorth-Hansen,Timothy P. Hughes,Jeroen Janssen,Hagop M. Kantarjian,Dong-Wook Kim,Richard A. Larson,Jeffrey H. Lipton,Francois-Xavier Mahon,Jiří Mayer,Franck E. Nicolini,Dietger Niederwieser,Fabrizio Pane,Jerald P. Radich,Delphine Rea,Johan Richter,Gianantonio Rosti,Philippe Rousselot,Giuseppe Saglio,Susanne Saußele,Simona Soverini,Juan Luis Steegmann,Anna G. Turkina,Andrey Zaritskey,Ruediger Hehlmann +33 more
TL;DR: An expert panel to critically evaluate and update the evidence to achieve goals to achieve a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR) in chronic myeloid leukemia.
Journal ArticleDOI
Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial.
Andreas Hochhaus,Giuseppe Saglio,Timothy P. Hughes,Richard A. Larson,Dong-Kee Kim,Surapol Issaragrisil,P. le Coutre,Gabriel Etienne,Pedro Enrique Dorlhiac-Llacer,Richard E. Clark,Ian W. Flinn,Hirohisa Nakamae,Breanne Donohue,Weiping Deng,Darshan Dalal,Hans D. Menssen,Hagop M. Kantarjian +16 more
TL;DR: Long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP, and few deaths in any arm were associated with CVEs, infections or pulmonary diseases.
Journal ArticleDOI
Long-Term Follow-Up of the French Stop Imatinib (STIM1) Study in Patients With Chronic Myeloid Leukemia
Gabriel Etienne,Joelle Guilhot,Delphine Rea,Françoise Rigal-Huguet,Franck E. Nicolini,Aude Charbonnier,Agnès Guerci-Bresler,Laurence Legros,Bruno Varet,Martine Gardembas,Viviane Dubruille,Michel Tulliez,Marie-Pierre Noel,Jean-Christophe Ianotto,Bruno Villemagne,Martin Carre,François Guilhot,Philippe Rousselot,Francois-Xavier Mahon +18 more
TL;DR: With a median follow-up of more than 6 years after treatment discontinuation, the STIM1 study demonstrates that IM can safely be discontinued in patients with a sustained deep molecular response with no late MR.
Journal ArticleDOI
Chronic Myeloid Leukaemia
TL;DR: This Seminar summarises the presentation, pathophysiology, diagnosis and monitoring technology, treatment options, side-effects, and outcomes of chronic myeloid leukaemia, and discusses the possibility of cure-ie, stable undetectable or low level disease in the absence of medication.
References
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A Class of $K$-Sample Tests for Comparing the Cumulative Incidence of a Competing Risk
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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
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Journal ArticleDOI
European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013
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 A. Schiffer,Richard T. Silver,Bengt Simonsson,Juan Luis Steegmann,John M. Goldman,Rüdiger Hehlmann +31 more
TL;DR: Optimal responders to chronic myeloid leukemia treatment should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved.
Journal ArticleDOI
Nilotinib versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia
Giuseppe Saglio,Dong-Wook Kim,Surapol Issaragrisil,Gabriel Etienne,Clarisse Lobo,Ricardo Pasquini,Richard E. Clark,Andreas Hochhaus,Timothy P. Hughes,Neil Gallagher,Albert Hoenekopp,Mei Dong,Ariful Haque,Richard A. Larson,Hagop M. Kantarjian +14 more
TL;DR: Nilotinib at a dose of either 300 mg or 400 mg twice daily was superior to imatinib in patients with newly diagnosed chronic-phase Philadelphia chromosome-positive CML, and no patient with progression to the accelerated phase or blast crisis had a major molecular response.
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