Response rates to imatinib mesylate (Gleevec) tablets continue to increase substantially over time while the yearly risk of progression to advanced disease continues to decline the longer patients take the medicine, according to 5-year data from a landmark study in patients with a form of life-threatening chronic myeloid leukemia (CML). Results of the International Randomized Interferon vs STI571 (IRIS) study were presented at the 2006 annual meeting of the American Society of Clinical Oncology in Atlanta. Data from the IRIS study, the largest clinical trial to date for newly diagnosed adult patients with Philadelphia chromosome-positive (Ph+) CML in chronic phase, showed the overall survival rate at 5 years to be 89.4% (range: 86%-92%) for patients receiving imatinib. This considers deaths from all causes, but only 4.6% of the patients died from causes related to leukemia. Before imatinib was available, about 50% of patients progressed to the more advanced stages of Ph+ CML after only 3 to 5 years, and survival was generally short for those patients.

Better Outcomes With Longer Therapy

The results of this phase III trial, which was started in June 2000, also showed that the proportion of patients with a complete cytogenetic response increased from 69% to 87% between the first and fifth years of treatment. Moreover, the yearly risk of progressing to advanced disease continued to decline—to 0.6% in the fifth year.

"Very few oncology medicines offer patients the opportunity to achieve better outcomes the longer they take the therapy," said David Epstein, president of Novartis Oncology. "That Gleevec demonstrates these significant improvements with long-term use is a good sign science will provide the path to turn lethal cancers into potentially manageable conditions with durable, well-tolerated targeted therapies." An estimated 93% of imatinib patients in the early, chronic phase of CML did not progress to the rapidly lethal advanced stages of the disease, and an estimated 83% survived with no evidence of disease progression at all at the 5-year follow-up.

IRIS Study

The IRIS study is an open-label phase III clinical trial enrolling 1,106 newly diagnosed patients with Ph+ CML in chronic phase in 177 centers across 16 countries. There are two arms to the study: one group of patients receiving imatinib, 400 mg/d, and another receiving a target dose of interferon of 5 MIU/m²/d in combination with cytarabine, 20 mg/m²/d for 10 days each month. Because of tolerability problems or lack of response to treatment, 69% of patients in the interferon/cytarabine arm crossed over to the imatinib arm, whereas only 3% of patients in the imatinib arm crossed over to the interferon/cytarabine arm.

Cumulative best responses to imatinib treatment improved significantly between the first and fifth years of treatment. Over that period, complete hematologic responses rose from 96% to 98%, major cytogenetic responses rose from 85% to 92% and complete cytogenetic responses rose from 69% to 87%.