Glivec/Gleevec may be effective in rare blood disease treatment
BASEL, SWITZERLAND -- The Novartis drug Glivec (imatinib) -- known as Gleevec in the U.S. -- may have efficacy in certain patients with hypereosinophilic syndrome (HES), according to a case report from researchers at the Mayo Clinic and Foundation, and the University of Utah. The report is published in the 4 May 2002 issue of "The Lancet" (UK).
HES is a very rare group of myeloproliferative disorders of unknown origin, characterised by the persistent overproduction of eosinophils (a type of white blood cell that is involved in a variety of functions, including defense against parasitic infection and allergic responses). HES is most commonly diagnosed in male patients aged 20-50 years. The symptoms can appear suddenly and dramatically, and can involve virtually any organ system, but more often they are insidious.
Typically, patients with HES have no detectable chromosomal abnormality. Notoriously difficult to manage, HES is often treated with the same therapies used to treat chronic myeloid leukemia (CML). This led the researchers to hypothesise that HES patients might respond to Glivec, a novel agent that has demonstrated unprecedented cytogenetic response rates in CML.
"Glivec is a targeted signal transduction inhibitor. Although the mechanism by which the drug exerts its effects on HES is unclear, Novartis is encouraged by the preliminary data which suggest that Glivec may play a role in treating these patients," said David Parkinson, M.D., Vice President, Novartis Oncology. "Novartis will monitor and investigate potential activity in this area."
Glivec inhibits the activity of certain enzymes, called tyrosine kinases, which play an important role within certain cancer cells. In CML, for example, it inhibits BCR-ABL, a by-product of the specific chromosomal abnormality, the Philadelphia chromosome, which characterises the disease in most patients. In gastrointestinal stromal tumours (GISTs), Glivec has been shown to inhibit the c-kit tyrosine kinase, and In vitro, Glivec has also been shown to inhibit PDGF-R (platelet derived growth factor receptors). Novartis is investigating the efficacy of Glivec, alone and in combination with other therapies, in a range of diseases in which these tyrosine kinases play a role.
In most countries where it is approved, Glivec is indicated for the treatment of patients with Philadelphia chromosome-positive CML in the blast crisis, accelerated phase or in chronic phase after failure of interferon-alpha therapy. The effectiveness of Glivec is based on overall haematological and cytogenetic response rates.
'Gleevec' has been approved for the CML indication in the United States, the European Union and more than 60 countries. In the U.S. and in Switzerland, it is approved for the treatment of patients with Kit (CD 117) positive unresectable (inoperable) and/or metastatic malignant gastrointestinal stromal tumours (GISTs). The Committee for Proprietary Medicinal Products (CPMP) in the EU issued a positive opinion for the GIST indication in February 2002, and approval is expected shortly.
Posted: April 2002