Three months is too soon to judge a CML patient's response to Gleevec, researchers find

December 06, 2003

SAN DIEGO, Calif. -- Gleevec has been shown to wipe out leukemia cells in 75 percent of the chronic myeloid leukemia (CML) patients who are treated with it. What oncologists haven't known is how long patients should take Gleevec before its effectiveness can be gauged. A new study to be presented at the American Society of Hematology (ASH) 45th Annual Meeting on Monday, Dec. 8, sheds light on the question.

"This data tells us how long a patient should take Gleevec before we measure how well it's fighting the CML. This is important in helping us know when during treatment to decide if Gleevec is the best treatment or if a new approach would be better," said Brian Druker, M.D., the study's lead author. He is the JELD-WEN Chair of Leukemia Research at the OHSU Cancer Institute and an investigator of the Howard Hughes Medical Institute.

Druker studies the molecular origin of CML as a means to develop the most effective treatments. Using this approach, Druker developed Gleevec to treat CML, a malignant cancer of the bone marrow in which the body overproduces cancerous white blood cells. Gleevec targets the cancer cells while leaving normal cells unharmed, producing little or no side effects. The blood counts of virtually all CML patients treated with the drug have returned to normal.

For this study, researchers sought to determine how long Gleevec should be given to accurately gauge a patient's response. To accomplish this, they examined data from a randomized study of 553 newly diagnosed chronic phase patients comparing Gleevec, also known as imatinib, with traditional combination therapy (interferon and cytosine arabinoside).

Scientists first studied whether a CML patient's response to Gleevec is related to a patient's survival without progression of the disease. To do this, they measured the cytogenetic response, which, in this case, refers to how many bone marrow cells contain the Philadelphia chromosome. The Philadelphia chromosome is a molecular abnormality unique to CML cells. The fewer blood cells that test positive for it, the better the cytogenetic response.

For this study, researchers defined disease progression as blood counts no longer being controlled by Gleevec, loss of a cytogenetic response, advancement to accelerated phase or blast crisis, or death during treatment.

Researchers found that achieving a complete cytogenetic response, which refers to the Philadelphia chromosome disappearing altogether from a patient's blood cells, had a significant impact on a patient's long-term outcome regardless of when it occurred in treatment. Patients whose cytogenetic response was complete were least likely to experience disease progression.

Interestingly, the length of treatment needed to reach a complete response had no effect on survival. Survival without disease progression at 24 months was 96 percent for patients with a complete response within the first three to six months, and 93 percent for those who achieved a complete response only after six months.

Researchers also looked at which patients were likely to have a complete response to Gleevec. Patients who were 35 percent Philadelphia chromosome positive or less at any time during treatment often had a complete response. Patients who were greater than 95 percent Philadelphia chromosome positive at three months still had nearly a 50 percent chance of subsequently obtaining a complete response. However, patients who were greater than 95 percent Philadelphia chromosome positive after six months or more of therapy had no more than a 14 percent chance of achieving a complete response.

Thus, three months is too soon to judge a response to Gleevec. On the other hand, patients who are greater than 95 percent Philadelphia chromosome positive at six months may be candidates for other treatment options.

Researchers are further analyzing the data to find out if increasing the dose of Gleevec improves the likelihood of a major or complete response to the drug.

Druker will present the study (Abstract 634, Probability and Impact of Obtaining a Cytogenetic Response to Imatinib as Initial Therapy for Chronic Myeloid Leukemia in Chronic Phase) on Monday, Dec. 8, at 3:30 p.m. PST at the ASH 45th Annual Meeting in San Diego.

Gleevec also is an approved, effective treatment for gastrointestinal stromal tumors, a form of intestinal cancer that previously was often fatal. Earlier this year an editorial published in the New England Journal of Medicine dubbed Gleevec the "gold standard" treatment for CML, and the drug became the frontline therapy. Gleevec also earned the FDA's approval for use in children, the first new pediatric cancer drug treatment in more than a decade. Recent studies also have found Gleevec to be effective in treating hypereosinophilic syndrome, a rare and often fatal blood disorder.
Note: A photo of Druker is available at

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