Journal ArticleDOI
Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial
Francois-Xavier Mahon,Delphine Rea,Joelle Guilhot,François Guilhot,Françoise Huguet,Franck E. Nicolini,Laurence Legros,Aude Charbonnier,Agnès Guerci,Bruno Varet,Gabriel Etienne,Josy Reiffers,Philippe Rousselot +12 more
TLDR
Imatinib discontinuation in this setting yields promising results for molecular relapse-free survival, raising the possibility that, at least in some patients, CML might be cured with tyrosine kinase inhibitors.Abstract:
Summary Background Imatinib treatment significantly improves survival in patients with chronic myeloid leukaemia (CML), but little is known about whether treatment can safely be discontinued in the long term. We aimed to assess whether imatinib can be discontinued without occurrence of molecular relapse in patients in complete molecular remission (CMR) while on imatinib. Methods In our prospective, multicentre, non-randomised Stop Imatinib (STIM) study, imatinib treatment (of >2 years duration) was discontinued in patients with CML who were aged 18 years and older and in CMR (>5-log reduction in BCR–ABL and ABL levels and undetectable transcripts on quantitative RT-PCR). Patients who had undergone immunomodulatory treatment (apart from interferon α), treatment for other malignancies, or allogeneic haemopoietic stem-cell transplantation were not included. Patients were enrolled at 19 participating institutions in France. In this interim analysis, rate of relapse was assessed by use of RT-PCR for patients with at least 12 months of follow-up. Imatinib was reintroduced in patients who had molecular relapse. This study is registered with ClinicalTrials.gov, number NCT00478985. Findings 100 patients were enrolled between July 9, 2007, and Dec 17, 2009. Median follow-up was 17 months (range 1–30), and 69 patients had at least 12 months follow-up (median 24 months, range 13–30). 42 (61%) of these 69 patients relapsed (40 before 6 months, one patient at month 7, and one at month 19). At 12 months, the probability of persistent CMR for these 69 patients was 41% (95% CI 29–52). All patients who relapsed responded to reintroduction of imatinib: 16 of the 42 patients who relapsed showed decreases in their BCR–ABL levels, and 26 achieved CMR that was sustained after imatinib rechallenge. Interpretation Imatinib can be safely discontinued in patients with a CMR of at least 2 years duration. Imatinib discontinuation in this setting yields promising results for molecular relapse-free survival, raising the possibility that, at least in some patients, CML might be cured with tyrosine kinase inhibitors. Funding French Ministry of Health (Programme Hospitalier de Recherche 2006 grants), Institut National du Cancer (INCA).read more
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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.
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Clinical practice guidelines in oncology
William J. Gradishar,Benjamin O. Anderson,Ron Balassanian,Sarah L. Blair,Harold J. Burstein,Amy E. Cyr,Anthony D. Elias,William B. Farrar,Andres Forero,Sharon H. Giordano,Matthew P. Goetz,Lori J. Goldstein,Steven J. Isakoff,Janice A. Lyons,P. Kelly Marcom,Ingrid A. Mayer,Beryl McCormick,Meena S. Moran,Ruth O'Regan,Sameer A. Patel,Lori J. Pierce,Elizabeth C. Reed,Kilian E. Salerno,Lee S. Schwartzberg,Amy Sitapati,Karen L. Smith,Mary Lou Smith,Hatem Soliman,George Somlo,Melinda L. Telli,John H. Ward,Rashmi Kumar,Dorothy A. Shead +32 more
TL;DR: This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.
Journal ArticleDOI
Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study
David M. Ross,Susan Branford,John F. Seymour,Anthony P. Schwarer,Christopher Arthur,David T Yeung,David T Yeung,Phuong Dang,Jarrad M. Goyne,Cassandra Slader,Robin Filshie,Anthony K. Mills,Junia V. Melo,Junia V. Melo,Deborah L. White,Deborah L. White,Andrew Grigg,Timothy P. Hughes,Timothy P. Hughes +18 more
TL;DR: The results confirm the safety and efficacy of a trial of imatinib withdrawal in stable UMRD with frequent, sensitive molecular monitoring and early rescue of molecular relapse, and show persistence of the original CML clone in all patients with stable U MRD, even several years after imatinIB withdrawal.
Journal ArticleDOI
Life Expectancy of Patients With Chronic Myeloid Leukemia Approaches the Life Expectancy of the General Population
Hannah Bower,Magnus Björkholm,Paul W. Dickman,Martin Höglund,Paul C. Lambert,Therese M.-L. Andersson +5 more
TL;DR: Imatinib mesylate and new TKIs along with allogeneic stem cell transplantation and other factors have contributed to the life expectancy in patients with CML approaching that of the general population today.
Journal ArticleDOI
Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION)
Hagop M. Kantarjian,Neil P. Shah,Jorge E. Cortes,Michele Baccarani,Mohan B. Agarwal,Maria Soledad Undurraga,Jianxiang Wang,Juan Julio Kassack Ipiña,Dong-Wook Kim,Michinori Ogura,Carolina Pavlovsky,Christian Junghanss,Jorge Milone,Franck E. Nicolini,Tadeusz Robak,Jan Van Droogenbroeck,Edo Vellenga,M. Brigid Bradley-Garelik,Chao Zhu,Andreas Hochhaus +19 more
TL;DR: Primary data showed superior efficacy for dasatinib compared with imatinib after 12 months, including significantly higher rates of complete cytogenetic response (CCyR), confirmed CCyR (primary end point), and major molecular response (MMR).
References
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Efficacy and Safety of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid Leukemia
Brian J. Druker,Moshe Talpaz,Debra Resta,Bin Peng,Elisabeth Buchdunger,John Ford,Nicholas B. Lydon,Hagop M. Kantarjian,Renaud Capdeville,Sayuri Ohno-Jones,Charles L. Sawyers +10 more
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Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia
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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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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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Granulocyte-Macrophage Progenitors as Candidate Leukemic Stem Cells in Blast-Crisis CML
Catriona Jamieson,Laurie Ailles,Scott J. Dylla,Manja Muijtjens,Carol D. Jones,James L. Zehnder,Jason Gotlib,Kevin Li,Markus G. Manz,Armand Keating,Charles L. Sawyers,Irving L. Weissman +11 more
TL;DR: Activation of beta-catenin in CML granulocyte-macrophage progenitors appears to enhance the self-renewal activity and leukemic potential of these cells.
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