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Results from the IRIS trial (The International Randomized Study of Interferon versus STI-571) were presented here this week at the American Society of Hematology.
A greater than 3 log reduction in leukemia load as measured by quantitative polymerase chain reaction (PCR) was achieved after 12 months of therapy in 39 percent of imatinib patients versus 2 percent of interferon cytarabine arabinoside (Ara-C) patients (p<0.001), according to the study authors.
The investigators followed 313 subjects with CML — 284 of whom received imatinib, and 29 of whom received IFN. They measured the BCR-ABL gene transcript level in blood of patients who achieve complete cytogenetic remission, defined as 0 percent Ph-positive cells in the marrow.
This research was a continuation of the IRIS study in which imatinab at a dose of 400 mg/day was compared to alpha interferon plus intermittent low dose cytarabine (IFN) as first-line therapy for CML in chronic phase. At 12 months, 68 percent of patients on imatinib achieved complete cytogenic remission compared to 7 percent on IFN. Blood testing was performed at one of three central laboratories at the time of complete cytogenic remission and every three months in follow-up.
The investigators normalized the BCR-ABL value to the BCR transcript level in order to compensate for RNA quality variations. They calculated the percentage ratio of BCR-ABL/BCR. PCR results were standardised at the laboratories.
Investigators at each laboratory calculated median BCR-ABL/BCR percent value of samples collected pre-study in 30 chronic phase patients, and developed PCR values relative to this standard baseline. Quicker achievement of complete cytogenic remission among patients receiving imatinib meant that 40 percent had three or more quantitative PCR evaluations after complete cytogenic remission, compared to 7 percent of patients receiving cytarabine.
Investigators analyzed the quantitative PCR test results from the date of complete cytogenic remission and from the date of entering the study.
"At time of complete cytogenic remission, the median log reduction from baseline in BCR-ABL/BCR percent values were 2.6 (imatinib) and 2.3 (IFN). Although the median values were similar, 32 percent of patients receiving imatinib had achieved a greater than 3 log reduction versus 0 percent IFN patients."
Of the 18 patients on imatinib who were followed for more than 12 months after complete cytogenic remission, 94 percent had a greater than 3 log reduction, the researchers report.
They also noted that, "Quantitative polymerase chain reaction studies after 12 months of treatment in patients who had achieved complete cytogenic remission showed a greater than 3 log decrease in 58 percent of those on IFN versus 26 percent of those on IFN/Ara-C (p=0.004)."
Extrapolating this using the overall complete cytogenic remission rates, a greater than 3 log reduction in BCR/ABL levels was achieved in 39 percent of all patients on imatinib but only 2 percent of all IFN patients. Thirteen percent of patients imatinib achieved a greater than 4 log reduction by 12 months on trial. Nine out of 294 patients on imatinib (3 percent) had greater than 4.5 log reductions confirmed in a second laboratory.
The research was supported by Novartis Pharmaceuticals.
*In 1960, in Philadelphia, researchers noted that chromosome 22 was abnormally small in patients with CML. This abnormal chromosome was named the 'Philadelphia chromosome'. In 1973, researchers found that the reason for this was that some of the genetic material of chromosome 22 had been swapped with some from chromosome 9; the ABL gene on chromosome 9 moves into the BCR gene on chromosome 22. The result the BCR-ABL gene that codes for a protein very similar to ABL. ABL normally makes a protein important for cell division. BCR-ABL works in a similar way but its activity is increased. As a result, the white cells in CML keep dividing in an uncontrolled way.
Source: Doctor's Guide
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