Leukemia Drug Proves Safe And Effective Over The Long Term, Study Suggests

A team of researchers from the U.S. and Europe, including the drug's creator, Brian Druker, MD, followed 454 patients with chronic-phase CML taking imatinib for more than six years. Prior to enrollment, all study participants had experienced either treatment failure or intolerance with interferon alpha, which was the standard of care for CML at the time the study was initiated.

"The long-term follow-up results of imatinib in CML post interferon failure reassure us of the high efficacy of the drug and its safety," stated Hagop Kantarjian, MD, the lead author on the study and Chairman and Professor of the Leukemia Department at the University of Texas M.D. Anderson Cancer Center. "With a six-year follow-up, the estimated six-year survival rate is 76 percent. In historical data, after interferon failure the average survival was about three to four years."

Imatinib dosage began at 400 milligrams per day and was escalated to 600 mg/d or 800 mg/d in patients who did not achieve positive treatment responses within set time periods or whose disease relapsed.

The best possible treatment outcome -- a complete cytogenetic response, which is the elimination of the genetic abnormality associated with the disease -- occurred in 57 percent of the study participants and was achieved in a median time of eight months. Overall survival rates and avoidance of disease progression were strongly correlated with cytogenetic response by 12 months; those with a minimal or no cytogenetic response within the first year faired poorly.

The incidence of serious side effects was low and, although 15 cases of heart dysfunction were reported in study participants, only four cases were considered to be drug-related. During the study, 35 patients discontinued the drug because of adverse events or abnormal test results.

"About half of the patients on the study continue to receive imatinib and 40 percent are in complete cytogenetic response," said Dr. Kantarjian. "No long-term new toxicities have been observed. In particular, the drug-related cardiac toxicity, which was reported to be of concern last year, was quite rare."

This clinical trial was the basis for the first approval of imatinib for CML, which has since become the standard of care for the disease.