Gleevec Effective as First-Line Therapy of CML: IRIS Trial

ASCO—In a phase III study, imatinib mesylate (Gleevec), formerly known as STI571, 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.

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 marrow transplantation.

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 to www.spirit-cml.org.