SAN FRANCISCO—Results of a phase II, open-label, multicenter study show that the investigational agent STI571 holds promise for many patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) whose disease has proved resistant to interferon therapy.

After 6 months of STI571 therapy, 56% of patients experienced a major cytogenetic response, Hagop Kantarjian, MD, said at the 42^nd Annual Meeting of the American Society of Hematology (ASH). The study was sponsored by Novartis Oncology, which has named the new agent Glivec.

A total of 532 patients were enrolled in the study from 28 centers in the United States, France, Germany, Italy and the United Kingdom, said Dr. Kantarjian, professor of medicine, Department of Hematology, M.D. Anderson Cancer Center. STI571 was administered orally at a dose of 400 mg daily.

Interferon failure was defined as a lack of complete hematologic response despite 3 months of an interferon-containing regimen, or as a lack of a cytogenetic response despite 1 year of an interferon-containing regimen. Patients who had suffered a hematologic or cytogenetic relapse were also included, as were patients with documented grade 3 interferon intolerance.

Among 388 patients treated with STI571 for 3 months, Dr. Kantarjian said, more than 90% achieved a complete hematologic response (ie, normalization of white blood cell counts), most within 4 to 6 weeks. Of these patients, 37% also achieved an overall major cytogenetic response: 13% had a complete cytogenetic response (0% Ph+ cells), and 23% had a partial response (less than 35% Ph+ cells).

He also reported preliminary data on 290 patients who have completed 6 months of STI571 therapy. Among these patients, 56% have had a major cytogenetic response, with a complete cytogenetic response rate of 28%.

Among patients with less aggressive disease (less than 100% Ph+ cells), 78% had a major cytogenetic response. Patients who began STI571 treatment earlier in their disease (within a year of diagnosis) had a major cytogenetic response rate of 62%.

"There was a concern that these cytogenetic responses might not be durable," Dr. Kantarjian said. "But, in fact, that has not been the case. There have been no patients with a cytogenetic response who have evolved into blast crisis."

Dr. Kantarjian also noted that older patients responded as well as the younger patients. (The median age in the study was 56 years). "Given the toxicity of interferon in the older age groups, STI571 should become the treatment of choice in these older patients," he said.

The most frequent adverse events in the study were nausea, muscle cramps, headache, vomiting, fatigue, and diarrhea. Grade 3-4 toxicities, including myelosuppression, were unusual, Dr. Kantarjian said, and occurred in only about 3% of patients.

"These results are better than anything we’ve ever had in patients with CML who had failure of interferon therapy," Dr. Kantarjian said. "The official conclusion is that the data are very encouraging and that the side effects are acceptable. But I would also like to express my personal opinion that this is the most important drug we have ever discovered for CML. Especially with patients treated early in their disease with STI571, we are going to have results beyond any previous expectations. I believe it should become front-line therapy."