Not so NICE for CML

Abstract

Imatinib (previously STI571) seems to be a very remarkable contribution to the management of chronic myeloid leukaemia (CML). It is thought to act by inhibiting the kinase activity of the BCR-ABL oncoprotein, which is deemed to cause the chronic phase of CML. Phase I clinical studies began in 1998 and it became rapidly apparent that the drug reverses symptoms and controls the leucocyte count in most CML patients in the chronic phase.1Druker BJ Talpaz M Resta DJ et al.Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia.N Engl J Med. 2001; 344: 1031-1037Crossref PubMed Scopus (4393) Google Scholar, 2Kantarjian H Sawyers C Hochhaus A et al.Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia.N Engl J Med. 2002; 346: 645-652Crossref PubMed Scopus (1811) Google Scholar Most importantly, it lowers the proportion of Philadelphia-chromosome-positive leukaemia cells in bone marrow to a much greater extent than any other therapeutic agent, and thus raises the possibility that some patients may prove eventually to be cured. It also has activity in the advanced phases of CML. These and other observations led to unusually rapid approval for its use in the USA by the Food and Drug Administration (FDA); the European Medicines Evaluation Agency approved its use in patients with CML in advanced phases and for chronic-phase patients deemed to have failed treatment with interferon-alfa, which was ratified in the UK in November, 2001. More than 15 000 patients have now been treated with this drug. Haematologists worldwide regard it as a major advance in the management of CML. However, patients have a median survival of 4–7 years, and it is far too early to say whether imatinib prolongs survival compared with other methods of treatment. For this reason the FDA required the manufacturers to undertake a prospective phase III study comparing imatinib with the combination of interferon-alfa and cytarabine in previously untreated CML patients. Preliminary results of this study were reported at the May meeting of the American Society of Clinical Oncology. Two-thirds of the patients treated with imatinib achieved complete cytogenetic remission. Progression-free survival at 1 year was significantly better in the imatinib group than in the interferon-alfa and cytarabine group (97·2 vs 80·3%, p<0·001), although overall survival was similar in the two groups, as would be expected with short follow-up. Against this background the National Institute for Clinical Excellence (NICE), which advises health authorities in England and Wales on the cost-effectiveness of drugs and techniques used in the National Health Service, has issued a preliminary appraisal consultation document recommending that imatinib should be funded only for patients in accelerated-phase disease and not for those in the chronic phase or in blastic transformation.3NICEAppraisal Consultation Document: imatinib for chronic myeloid leukaemia.http://www.nice.org.uk/article.asp?a=31915Google Scholar The NICE Appraisal Committee bases this advice on the current lack of robust survival data and the results of pharmacoeconomic analyses, in which imatinib was not better than other cheaper drugs. By contrast, the Scottish Medicines Consortium (and other European bodies) recommend funding for imatinib in all phases of CML in accordance with the product licence.4The Scottish Medicines Consortium advises on imatinib mesylate (Glivec)http://www.htbs.co.uk/smc/press/index.asp?did=532Google Scholar We believe that the current NICE recommendations ignore the probability that imatinib will prolong survival for CML patients by a substantial number of years. In recommending that patients await the results of further randomised prospective studies, which, in view of available clinical data, will prove very difficult to design and even more difficult to implement, NICE is in grave danger of denying CML patients the benefit of a potentially invaluable drug. We earnestly hope that the Appraisal Committee will reconsider its preliminary recommendations.