myeloid leukemia (CML) is a cancer of blood cells where the bone marrow is
replaced with malignant leukemic cells. CML is usually associated with a
chromosome abnormality called the Philadelphia chromosome
. An abnormal
genetic exchange occurs resulting in a gene called BCR-ABL. This gene codes for
a protein that leads to uncontrolled cell growth (cancer) because of
tyrosine kinase activity
. The drug Imatinib
has been the first-line
therapy for everyone with CML. It inhibits the activity of tyrosine kinase.
However, in some patients, the response to this drug is not optimal. The
standard dose of the drug is 400mg. A recent randomised study compared the
standard dose of Imatinib with higher doses or a combination of imatinib
with cytarabine or peginterferon alfa-2a
as treatment for newly diagnosed,
chronic-phase CML. Treatment with
imatinib and peginterferon alfa-2a was associated with significantly higher
rates of molecular responses in people with CML.
is a drug with dual mode of action - both antiviral and on the immune system
This drug has been widely used in the treatment of Hepatitis C and Hepatitis B.
The addition of peginterferon alfa-2a to imatinib in patients with CML may
reduce the risk of progression and may be associated with long-term survival. Studies
suggest that it is important to combine the agents for at least 12 months.
The combination is however associated with substantial toxic
effects that often result in the discontinuation of peginterferon alfa-2a. A
lower dose of peginterferon alfa-2a (e.g., 45 μg per week) might allow the
combination to be given for a longer period. Imatinib-peginterferon alfa-2a
combination brings a faster response than the known second-generation tyrosine
kinase inhibitors such as dasatinib or nilotinib. Therapy with with imatinib
alone may lead to the persistence of leukemic cells. Only a minority of patients
treated with imatinib have a complete molecular remission. The addition of
peginterferon alfa-2a may increase the efficacy of tyrosine kinase inhibitors.
In conclusion, combining imatinib to peginterferon alfa-2a has
been found to bring a better response as suggested by randomised studies
. A follow-up on CML patients
using imatinib shows an overall survival rate of 89% after five years.
The New England Journal of Medicine