A new treatment for patients with chronic myeloid leukemia

Dec 5 2004

A new treatment for patients with chronic myeloid leukemia (CML) -- a disorder marked by an overproduction of white blood cells -- yields positive results in those who have relapsed on imatinib, the standard treatment for the disease, according to a Phase I study to be presented today at the 46th Annual Meeting of the American Society of Hematology (ASH).

"Five years ago, the plenary session at ASH heard the first announcement of an entirely new form of treatment for the disease CML. The drug, imatinib, was the first in a class of 'targeted therapeutic molecules' which act in a unique manner to destroy only the leukemic, and not normal, cells," said Stanley Schrier, M.D., Active Emeritus Professor of Medicine/ Hematology at Stanford University School of Medicine and President of the American Society of Hematology. "Literally overnight, imatinib became the standard of treatment for CML because it was relatively non-toxic, easy to administer, and worked fast to produce excellent clinical remissions. Inevitably, resistance to imatinib occurred and now ASH will hear about new agents designed to treat patients who no longer benefit from imatinib."

Researchers at the University of California Los Angeles (UCLA) School of Medicine and M.D. Anderson Cancer Center studied 29 patients in the early stages of CML who had experienced hematologic progression (a worsening of white blood cell levels) or intolerance while they were being treated with imatinib, more commonly known as Gleevec. The patients were provided with an investigational drug known as BMS-354825 in doses ranging from 15 to 180 mg per day taken orally five to seven days a week for up to nine months.

Of the original group, 26 patients were studied for greater than four weeks and, of those, 73 percent experienced a complete hematologic response, meaning the number of white blood cells was no longer out of control and the signs and symptoms of leukemia were gone. Those who experienced only a partial response are currently receiving higher doses of BMS-354825 in an effort to move them toward complete hematologic response.

More than half of those treated for a period greater than three months also experienced varying levels of cytogenetic response (the elimination of cells with the genetic cancer-causing defect), including one who experienced a complete cytogenetic response.

In addition to the positive clinical results, researchers found that the drug was extremely well-tolerated with virtually no side effects. Dose escalation continues, and phase II studies in chronic, accelerated, and blast crisis CML are currently being initiated.

According to Charles L. Sawyers, M.D., Professor of Medicine at the UCLA School of Medicine, and lead author of the study, "The results of this study provide compelling evidence supporting the safety and efficacy of treatment with BMS-354825 in patients whose chronic phase CML is resistant to standard treatment with imatinib. Additional data and continued patient follow-up, expected to strengthen these findings, will available by the time of the ASH annual meeting."