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European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013

Michele Baccarani1,*, Michael W. Deininger2, Gianantonio Rosti3, Andreas Hochhaus4, Simona Soverini3, Jane F. Apperley5, Francisco Cervantes6, Richard E. Clark7, Jorge E. Cortes8, François Guilhot9, Henrik Hjorth-Hansen10, Timothy P. Hughes11, Hagop M. Kantarjian8, Dong-Wook Kim12, Richard A. Larson13, Jeffrey H. Lipton14, François-Xavier Mahon15, Giovanni Martinelli3, Jiri Mayer16, Martin C. Müller17, Dietger Niederwieser18, Fabrizio Pane19, Jerald P. Radich20, Philippe Rousselot21, Giuseppe Saglio22, Susanne Saußele17, Charles Schiffer23, Richard Silver24, Bengt Simonsson25, Juan-Luis Steegmann26, John M. Goldman27, and Rüdiger Hehlmann17

Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors (TKIs), mandate regular updating of concepts and management. An ELN expert panel reviewed prior and new studies, to update recommendations made in 2009. We recommend as initial treatment imatinib or nilotinib or dasatinib. Response is assessed with standardized RQ-PCR and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels ≤10% at 3 months, <1% at 6 months, and ≤0.1% from 12 months onward, define optimal response, while >10% at 6 months and >1% from 12 months onward define failure, mandating a change of treatment.

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"Treating Chronic Myeloid Leukemia Improving Management through understanding the patient experiences"

The Chronic Myelogenous Leukemia (CML) Society of Canada is pleased to provide open access to the paper, “Treating Chronic Myeloid Leukemia - Improving Management Through Understanding of the Patient Experience”.

The tremendous progress made in chronic myeloid leukemia (CML) treatment affords patients more options than ever. Five currently available BCR-ABL inhibitors form the mainstay of CML treatment, including first-generation imatinib and more potent second-generation BCR-ABL inhibitors dasatinib and nilotinib, with bosutinib and ponatinib having been recently approved for market inclusion. Studies show that dasatinib and nilotinib exhibit greater efficacy than imatinib in first-line chronic-phase CML (CML-CP), allowing more patients to achieve deeper, more rapid responses associated with improved outcomes.
With alternatives to imatinib for first-line CML-CP and the wealth of information (and misinformation) on the Internet, a tremendous need exists for clear, accurate facts to assist patients in making treatment decisions. Patients appreciate the guidance of their oncology nurse in providing disease, treatment, and monitoring information tailored to meet their needs. Oncology nurses who are able to clearly explain emerging data, including the meaning and significance of faster, deeper responses, will be a valuable resource to their patients.

The paper is written by Cheryl-Anne Simoneau, BA, who is the president and chief executive officer of the Chronic Myeloid Leukemia Society of Canada. Writing and editorial support were provided by Anita Engh, PhD, at Stem Scientific with funding from Bristol-Myers Squibb. The author takes full responsibility for the content of the article. The author did not receive honoraria for this work. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias.

Landmark analysis of 4-year (y) data from ENESTnd.

Impact of early molecular response to nilotinib (NIL) or imatinib (IM) on the long-term outcomes of newly diagnosed patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP)

2013 ASCO Annual Meeting
Abstract Number: 7054^
Citation: J Clin Oncol 31, 2013 (suppl; abstr 7054^)

Giuseppe Saglio, Timothy P. Hughes, Richard A. Larson, Surapol Issaragrilsil, Anna G. Turkina, Juan Luis Steegmann, Jose L. Lopez, Chiaki Nakaseko, Matt E. Kalaycio, Francoise Huguet, Charisse N. Kemp, Xiaolin Fan, Hans D. Menssen, Hagop M. Kantarjian, Andreas Hochhaus; University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy; Centre for Cancer Biology, SA Pathology, University of Adelaide, Adelaide, Australia; The University of Chicago, Chicago, IL; Mahidol University, Siriraj Hospital, Bangkok, Thailand; Hematology Research Center, Moscow, Russia; Hospital Universitario de la Princesa, Madrid, Spain; Banco Municipal de Sangre, Dpt. Clinicas Hematologicas, Esq. Pirineos, Caracas, DC, Venezuela; Chiba University Hospital, Department of Hematology, Chiba, Japan; Cleveland Clinic, Cleveland, OH; Hospital de Purpan, Toulouse, France; Novartis Pharmaceuticals Corp, East Hanover, NJ; Novartis Pharma AG, Basel, Switzerland; The University of Texas MD Anderson Cancer Center, Houston, TX; Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany

Background: ENESTnd demonstrated the superiority of NIL to IM in pts with newly diagnosed CML-CP, such as higher rates of molecular response (MR) and reduced risk of progression to accelerated phase (AP)/blast crisis (BC). This landmark analysis of ENESTnd is based on BCR-ABL transcript levels at 3 mo, with 4 y of follow-up.

Plasma trough imatinib levels and molecular response in patients with CML: A single institution study from India.

2013 ASCO Annual Meeting
Abstract Number: 7079
Citation: J Clin Oncol 31, 2013 (suppl; abstr 7079)
Hemant Malhotra, Pratibha Sharma, Shipra Bhargava, Om Singh Rathode, Bharti Malhotra, Vikram Gota; Birla Cancer Center, SMS Medical College Hospital, Jaipur, India; Advanced Research Lab, SMS Medical College, Jaipur, India; Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Center, Navi Mumbai, India

Background: One of the reasons proposed for suboptimal responses in Chronic Myeloid Leukemia (CML) patients receiving standard-dose Imatinib has been low blood levels of the drug. Our study aimed to determine the correlation between mean trough Imatinib plasma levels and molecular response in CML chronic phase patients at our centre. We also attempted to compare imatinib plasma levels in patients receiving Gleevec (Novartis) versus patients who were on the generic version of the drug.

How I Manage: Chronic Myeloid Leukemia by Jerald Radich, MD

" The tyrosine kinase inhibitors (TKIs) have irrevocably changed the care of chronic myeloid leukemia (CML) patients, dramatically changing the natural history of this disease.1-4 With multiple TKIs available, we now have an “embarrassment of riches” in treatment options. Below are some common questions and clinically relevant answers regarding treatment.

The choices are imatinib (Gleevec, Novartis) and the more potent second-generation TKIs nilotinib (Tasigna, Novartis) and dasatinib (Sprycel, Bristol-Myers Squibb). Here are some basic considerations for selecting therapy:........"

Targeting of the MNK–eIF4E axis in blast crisis CML inhibits leukemia stem cell function


Cancer stem cells (CSCs) frequently acquire the ability to self-renew and persist in their hosts by coopting normal stem cell programs. Blast crisis (BC) chronic myeloid leukemia is a prototypic example, as the acquired activation of β-catenin signaling that enables BC CSC function is also important in normal hematopoietic stem cell maintenance. In identifying eIF4E phosphorylation by the MNK kinases as a necessary step in β-catenin activation in BC CSCs, but not normal hematopoietic stem cells, we define a therapeutic target in BC. Our studies suggest that clinical trials with MNK kinase inhibitors are warranted in BC chronic myeloid leukemia.

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population study shows the advent of 2ndGen TKIs has improved progression-free survival in CML

Sebastian Francis, Claire Lucas, Steven Lane, Lihui Wang, Sarah Watmough, Katy Knight, Jo Bell, Mohammed Kaleel-Rahman, Edwin Lee, David O’Brien, Nauman M. Butt, Walid Sadik, Lally De Soysa, Jim R.C. Seale, Rahuman Salim, Richard E. Clark
Received 30 October 2012; published online 24 April 2013.

Population based data suggest the proportion of patients failing imatinib in chronic myeloid leukaemia (CML) is higher than the reported one-third of patients in clinical trials. Clinical trials have demonstrated second generation tyrosine kinase inhibitors (TKI) dasatinib and nilotinib can restore complete cytogenetic remission (CCR) and major molecular response (MMR) to many patients failing imatinib, but their impact in the general population is not clear.

Design and methods
We report CML outcome in a population of 2.3 million people in a geographically contiguous area of North West England and North Wales.

Between 2003 and 2009, 192 new CML cases were diagnosed, of whom 184 were in chronic phase and 160 started on imatinib. The maximal CCR rate was 65% at 24 months and the maximal MMR rate was 50% at 36 months. Patients diagnosed since second generation TKI became available for imatinib failure had a more rapid cumulative CCR and MMR rate and a significantly improved progression free survival (p=0.022) than those diagnosed before this time.

The study indicates that second generation TKI have improved CML outcome in the general population.


Early molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML

Susan Branford1,2,3, David T. Yeung1,2,4, David M. Ross2,4,5, Jodi A. Prime1, Chani R. Field1, Haley K. Altamura1, Alexandra L. Yeoman1, Jasmina Georgievski1, Bronte A. Jamison1, Stuart Phillis1, Brad Sullivan1, Nancy E. Briggs6, Mark Hertzberg7,8, John F. Seymour7,9, John Reynolds10, and Timothy P. Hughes2,4,7
+ Author Affiliations

Key Points

1. Independent predictors of stable, undetectable BCR-ABL1 during first-line imatinib therapy were female sex and the BCR-ABL1 value at 3 months.

2. Time to achieve an MMR influenced time to stable, undetectable BCR-ABL1, suggesting slower dynamics of BCR-ABL1 decline with delayed MMR.

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Dynamics of chronic myeloid leukemia response to long-term targeted therapy reveal treatment effects on leukemic stem cells

Min Tang1, Mithat Gonen2, Alfonso Quintas-Cardama3, Jorge Cortes3, Hagop Kantarjian3, Chani Field4, Timothy P. Hughes4, Susan Branford4, and Franziska Michor1

+ Author Affiliations
1Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, and Department of Biostatistics, Harvard School of Public Health, Boston, MA;2Department of Biostatistics and Epidemiology, Memorial Sloan-Kettering Cancer Center, New York, NY;3Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX; and4Department of Genetics and Molecular Pathology, SA Pathology, and University of Adelaide, Adelaide, Australia

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Price of drugs for chronic myeloid leukemia (CML), reflection of the unsustainable cancer drug prices: perspective of CML Experts

Blood First Edition Paper, prepublished online April 25, 2013; DOI 10.1182/blood-2013-03-490003

As a group of more than 100 experts in chronic myeloid leukemia (CML),
we draw attention to the high prices of cancer drugs, with the particular
focus on the prices of approved tyrosine kinase inhibitors for the treatment
of CML. This editorial addresses the multiple factors involved in cancer
drug pricing, their impact on individual patients and healthcare policies, and
argues for the need to lower the prices of cancer drugs to allow more
patients to afford them and to maintain sound long-term healthcare policies.

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