Guidance on the use of imatinib for chronic myeloid leukaemia

  • Technology appraisal guidance
  • TA70
  • Published: 
  • Last updated: 

Scope: Imatinib for Chronic Myeloid Leukaemia (first line therapy)

NATIONAL INSTITUTE FOR CLINICAL EXCELLENCE

Health Technology Appraisal

Imatinib for Chronic Myeloid Leukaemia (first line therapy)

Scope

 

Objective: to establish the clinical and cost effectiveness of imatinib in its proposed new indication (subject to licensing), for the first line treatment of newly diagnosed Philadelphia (Ph) chromosome positive Chronic Myeloid Leukaemia (CML) in the chronic phase, relative to current standard treatments, and to produce guidance to the NHS in England and Wales.1

Background: CML is one of the most common types of leukaemia in England and Wales, with the annual case rates of 1.2 per 100,000 men and 1.1 per 100,000 women in England and 1.63 and 0.67 respectively in Wales. In 1998 there were around 570 new cases of CML registered in England, and 30 in Wales, two thirds of which occurred in people over 60 years of age. 2

Approximately 95% of patients with CML have a chromosomal abnormality known as the Philadelphia (Ph) chromosome, or BCR-ABL transcripts. The abnormality associated with the Ph chromosome (and/or BCR-ABL transcripts) leads to abnormal tyrosine kinase activity, which influences cellular processes such as proliferation, differentiation and survival. Cells containing the abnormal gene and protein replicate quickly and may be protected from programmed cell death. They therefore become predominant, initially in the bone marrow and subsequently in the bloodstream, impairing the production of normal white cells.

The Institute is expected to issue guidance in September 2002, on imatinib use for second line treatment in adults with chronic phase CML who are intolerant of interferon-alpha (IFN-a) therapy or in whom IFN-a is deemed to have failed to control the disease, and as a first line treatment in adults with CML in the accelerated phase or blast-crisis.

Technology: Imatinib (Glivec, Novartis) is an oral signal transduction inhibitor, rationally designed to competitively inhibit BCR-ABL tyrosine kinase activity associated with Ph chromosome positive (and/or BCR-ABL positive) CML. By blocking specific signals in cells expressing the BCR-ABL protein, imatinib reduces the uncontrolled cellular proliferation of white blood cells that is a characteristic feature of CML.

Intervention(s)

Oral imatinib as first line treatment of newly diagnosed Philadelphia (Ph) chromosome positive chronic myeloid leukaemia in the chronic phase (subject to licensing)

Population(s)

Newly diagnosed patients with Ph chromosome positive (and/or BCR-ABL positive) CML in the chronic phase

Current standard treatments (comparators)

Interferon alpha (as monotherapy or in combination), bone marrow transplantation and conventional chemotherapy (with hydroxyurea or busulfan)

Other considerations

Survival and 'quality of life' are preferred end-points in terms of assessing effectiveness. However surrogate outcome measures such as cytogenetic response and haematological response will be considered, given that the association with survival has been clearly demonstrated.

If the evidence allows, the appraisal will attempt to identify the criteria for selecting patients for whom this treatment would be particularly appropriate.

The optimal duration of treatment should be defined.

Potential side effects should be identified.

 

1 The remit from the Department of Health/National Assembly for Wales was "To advise on the clinical and cost-effectiveness of imatinib (Glivec), relative to existing treatments, in its licensed indications for the first line treatment of chronic myeloid leukaemia"

2 ONS (2002) Cancer registrations statistics England, 1998. available from www.statistics.gov.uk Figures for Wales from the Welsh Cancer Surveillance and Intelligence Unit (WCSIU), Cardiff.

This page was last updated: 30 March 2010