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Newly Diagnosed Myeloid Leukemia Responds to Imatinib

Cod. A07022007

In a 5-year follow-up of patients with newly diagnosed CML, imatinib was superior to interferon-{alpha} plus cytarabine.

The dramatic efficacy of imatinib (Gleevec) in chronic myeloid leukemia (CML) patients has made it a paradigm for targeted cancer therapies. Researchers now provide 5-year follow-up data on patients who were treated in the phase III, industry-sponsored, IRIS study. Eleven hundred six patients with newly diagnosed CML were randomized to daily oral imatinib or the combination of interferon-{alpha} plus cytarabine. The primary endpoint was event-free survival; secondary endpoints were complete hematologic, cytogenetic, and molecular responses. Crossover was allowed for inadequate response to or toxicity of originally assigned therapy; 65% of patients crossed over to imatinib, whereas only 3% crossed over to interferon-{alpha} plus cytarabine. As a result, very few patients received long-term interferon, and this report focused on the imatinib-treated patients.

By 12 months, 96% of imatinib patients achieved complete hematologic responses, and 69% achieved complete cytogenetic responses; these rates were 98% and 87%, respectively, at 5 years. At 5 years, 89% of patients were alive, and 83% had experienced no disease-related events. The estimated annual rates of progression to accelerated phase or blast crisis decreased over time: 1.5% in year 1, 1.8% in year 2, 1.6% in year 3, 0.9% in year 4, and 0.6% in year 5. All patients who achieved complete cytogenetic responses and molecular responses (defined as >3 log reduction in BCR-ABL transcripts) survived at 5 years, without progression to accelerated phase or blast crisis. No difference in survival was noted between patients who were assigned initially to imatinib and those who crossed over to imatinib. Side effects of imatinib therapy included edema, muscle cramps or joint pain, diarrhea, and rash. One patient developed heart failure.

Comment: Only 7% of imatinib-treated patients progressed to accelerated phase or blast crisis. Risk for progression decreased over time and was <1% in years 4 and 5 of imatinib therapy; overall survival of imatinib-treated patients was 89%. These impressive results confirm imatinib as standard therapy for initial treatment of CML patients. As noted by the authors, the current recommendation is to continue therapy indefinitely, because relapses occur in some patients when treatment is discontinued. Ongoing questions relate to administration of higher initial doses of imatinib and integration of next-generation kinase inhibitors (i.e., dasatinib and nilotinib) into treatment algorithms. Safety and toxicity of long-term therapy still require assessment, especially in view of recent reports of cardiomyopathy and congestive heart failure in a small subset of patients.

— Michael E. Williams, MD

Published in Journal Watch Oncology and Hematology December 6, 2006