ORLANDO-In a phase III
study, imatinib mesylate (Gleevec),
formerly known as STI-571, produced
a 96% complete hematologic
response rate and a 68% complete
cytogenetic response rate in newly diagnosed
chronic myeloid leukemia
(CML) patients, Brian Druker, MD,
said on behalf of the IRIS (International
Randomized Interferon vs STI-
571) Study Group at the 38th Annual
Meeting of the American Society
of Clinical Oncology (abstract 1).
"This study shows that with the
right target and the right drug, you
can see remarkable results," Dr.
Druker said at a media briefing announcing
the results. Imatinib
mesylate, a specific inhibitor of the
Bcr-Abl tyrosine kinase, has previously
been proved effective in CML in advanced
stages and in patients who no
longer respond to interferon.
From June 2000 to January 2001,
the IRIS study enrolled 1,106 patients
at 177 centers in 16 countries. The patients,
all within 6 months of diagnosis
and in chronic phase, were randomized
to receive imatinib 400 mg/d or
interferon at a target dose of 5 MIU/
m2/d plus cytarabine arabinoside
(ara-C) at a dose of 20 mg/m2/d for
10 days per month.
Crossover was allowed for lack of
response, loss of response, a rapidly
increasing white blood cell count, or
severe intolerance of therapy. Median
follow-up was 14 months.
"We were astounded by how
much better the Gleevec patients
did," said Dr. Druker, professor of
medicine, Oregon Health & Science
University. In contrast to the 96%
complete hematologic response rate
seen with imatinib mesylate, the interferon
patients had a rate of 67%.
The imatinib mesylate patients
had an 83% major cytogenetic response
rate (68% complete), compared
with only 20% for the interferon/
cytarabine group (7% complete).
In addition, 23% of patients in
the interferon group could not tolerate
the therapy, compared with
0.7% of patients who were intolerant
to imatinib mesylate.
At 12 months, 7% of interferon
patients had progressed to accelerated
phase or blast crisis while on therapy
vs 1.5% of the imatinib mesylate
patients (P < .001). Of the imatinib
patients, 90% remain on therapy vs
30% of the interferon patients.
When asked about the high cost of
imatinib mesylate therapy-roughly
$25,000 per year-Dr. Druker pointed
out that patients on imatinib
mesylate can usually remain employed
and contributing to society because
of the lack of serious side effects,
whereas those on interferon are often
too sick to continue working.
New Cases: An estimated 30,800 new cases are expected in 2002,
approximately evenly divided between acute leukemia and chronic
leukemia. Although often thought of as primarily a childhood disease,
leukemia is diagnosed 10 times more often in adults than in children.
Acute lymphocytic leukemia accounts for approximately 2,000 of the
leukemia cases among children. In adults, the most common types are
acute myeloid leukemia (approximately 10,600 cases) and chronic
lymphocytic leukemia (approximately 7,000 cases). Incidence of acute
myeloid leukemia increased by 1.8% per year among males during
1992-1998, with most of the increase occurring in the elderly, possibly
attributable to cigarette smoking.
Adapted from: Cancer Facts & Figures, American Cancer Society, 2002.
He said that future studies of
imatinib mesylate in CML should
include use of higher doses, use in
combination with other therapies,
and use in comparison with bone
The discussant for the paper,
Stephen Mackinnon, MD, Department
of Haematology, University
College London, suggested that if the
responses prove durable, patients
taking imatinib mesylate might be
able to avoid bone marrow transplantation,
currently considered the
only cure for CML.
Dr. Mackinnon described a multinational
trial under development
known as SPIRIT (STI-571 Prospective
International Randomized Trial).
A planned 3,000 patients with
chronic phase CML diagnosed within
6 months will be randomized to
imatinib alone or in combination
with either interferon or cytarabine.
The primary endpoint will be 5-year
survival. For more information, go