In the circumstances we feel we have done all we can and that an appeal is not a
positive option for us. We feel our focus must now shift to ensuring that applications to the Cancer Drugs Fund are successful on every occasion a clinician selects that
option to access dasatinib for patients in need.

We continue to urge BMS to submit a Patient Access Scheme to the Department of Health.

Please read full statement here:

Clinical Care Options Oncology

Chronic Myeloid Leukaemia Treatment in Evolution: Recent Advances in Therapy. Moshe Talpaz, MD.
 
Key Concepts:
This educational activity is designed to provide a rapid review of essential practice relevant issues to quickly update busy clinicians
on recent data affecting the management of patients with chronic myeloid leukaemia (CML).
An interactive clinical vignette using a specific patient example has been incorporated into the discussion to illustrate a key point relevant
to today's clinic.
 
*  Extended follow up of 2 pivotal trials separately evaluating the more potent 2nd generation TKIs in the first line setting,
    demonstrates lower rates of transformation to accelerated phase or blast crisis compared with imatinib, an important goal
    due to the dismal prognosis following transformation.
*  Patient characteristics such as heart disease and gastrointestinal problems are critical to the choice of 2nd generations TKIs,
    with nilotinib being preferred in the former and dasatinib being preferred in the latter.
*  Bosutinib, an experimental TKI, showes modestly improved efficacy with more toxicity compared with imatinib as first line
    therapy for chronic phase CML.
*  Bostunib is approximately as active as nilotinib and dasatinib as 2nd line treatment, with activity in some Bcr-Abl mutations
    resistant to these two agents.
*  Ponatinib, another experimental TKI, produced high rates of major cytogenetic responses across subgroups of heavily
    pre-treated patients with CML, including those with the T315i mutation. ...read more

 
Abstract
The outcome of chronic myeloid leukemia (CML) has been profoundly changed by the introduction of tyrosine kinase inhibitors into therapy, but the prognosis of patients with CML is still evaluated using prognostic scores developed in the chemotherapy and interferon era.
The present work describes a new prognostic score that is superior to the Sokal and Euro scores both in its prognostic ability and in its simplicity.
The predictive power of the score was developed and tested on a group of patients selected from a registry of 2060 patients enrolled in studies of first-line treatment with imatinib-based regimes. ...read more

Not Only Response but Early Response to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia.  Jorge Cortes, January 2012

When I started my career in leukemia research, interferon alfa was standard therapy for patients with chronic myeloid leukemia (CML). Interferon could induce complete cytogenetic response

(CCyR; ie, 0% Philadelphia-chromosome metaphases) or partial cytogenetic response (PCyR; ie, 1% to 35%), and such responses were associated with improved survival. These responses, particularly CCyR, occurred only in a minority of patients and the time to response was not given much attention. With the introduction of tyrosine kinase inhibitors (TKIs), our goals became more ambitious, aiming for higher rates ofCCyR. For much ofthe early years ofthe TKI era, the common thought was that responses continued to occur with prolonged therapy and that 40% to 60% patients might still achieve CCyR at later times (even ifnot yet achieved during the first 12 months

of therapy). The thought at the time was that achieving a response was good enough, regardless of when it occurred. Indeed, some patients may achieve CCyR after 2 or 3 years on therapy, and some analyses suggest that time to response had limited impact in the long-term outcome of patients.  Options such as high-dose imatinib yielded higher rates of cytogenetic and molecular response and lower transcript levels at early time points, but in some studies, the response rates later became similar to those achieved with standard-dose imatinib. The value of these early responses was thus frequently questioned and considered a transient occurrence.

read full article.... http://jco.ascopubs.org/content/30/3/223.full.pdf

Purpose: ...read more

Chronic myeloid leukemia is a model of how the molecular understanding of a disease can provide the platform for therapy and diagnostics. Clinicians are now empowered with first- and second-generation tyrosine kinases, as well as molecular tools to monitor disease and characterize resistance. However, there are still unanswered questions regarding optimization of therapy, the utility of molecular monitoring, and the search (or need) of “cure” that bears thought. In this review, we will discuss these issues, as they provide a roadmap for what may lie ahead in the therapy of other hematologic malignancies, particular the other myeloproliferative syndromes, where specific genetic lesions, and targeted therapy, are now being realized.
http://asheducationbook.hematologylibrary.org/content/2010/1/122.full ...read more

Wendy T Parker, Musei Ho, Hamish S Scott, Timothy P Hughes, Susan Branford.
Specific imatinib-resistant BCR-ABL1 mutations (Y253H, E255K/V, T315I, F317L, F359V/C) predict failure of second-line nilotinib and/or dasatinib therapy in CML patients....
http://bloodjournal.hematologylibrary.org/content/early/2011/12/30/blood-2011-08-375535.abstract

CML Support Group: Response to the Appeal Panel judgement in favour of the NICE 
decision not to recommend dasatinib as a second line treatment option for imatinib
resistant CML and in patients intolerant to imatinib, and including its use in blast
phase CML.
 
We are disappointed, though not entirely surprised, at the outcome of the appeal
against the recommendations of this very lengthy and complex Multiple Technology
Appraisal : Dasatinib, high-dose imatinib and nilotinib for the treatment ...read more

Guidance: Patient version

Dasatinib, high-dose imatinib and nilotinib for chronic myeloid leukaemia:

This document is about when dasatinib, high-dose imatinib and 

nilotinib should be used to treat people with chronic myeloid leukaemia

that has not responded to imatinib or who cannot tolerate imatinib in the 

NHS in England and Wales. It explains guidance (advice) from NICE 

(the National Institute for Health and Clinical Excellence). It is written for 

people with chronic myeloid leukaemia but it may also be useful for their 

families or carers or for anyone with an interest in the condition...more
http://www.nice.org.uk/nicemedia/live/13645/57824/57824.pdf
------------------------------------------------------------------------------------------------
Full guidance: TA241
Dasatinib, high-dose imatinib and nilotinib for the treatment of imatinib-resistant chronic myeloid leukaemia (CML) (part review of NICE technology appraisal guidance 70), and dasatinib and nilotinib for people with CML for whom treatment with imatinib has failed because of intolerance
 

Issued: January 2012     

NICE technology appraisal guidance 241

more......

http://www.nice.org.uk/nicemedia/live/13645/57823/57823.pdf