Source: Leukemia  |  Posted 8 years ago

Patients in the chronic phase of chronic myeloid leukaemia (CML) who are treated with imatinib achieve a significantly superior molecular response, compared to those who are treated with interferon alfa plus cytarabine (IFN + AraC), according to findings from the IRIS trial.

Researchers from Australia, New Zealand and Switzerland led by Ms. S. Branford, Division of Molecular Pathology, Institute of Medical and Veterinary Science, South Australia, conducted a Phase 3 randomised study with 62 newly diagnosed patients in the chronic-phase of CML.

Four patients withdrew from the study after 3 months of therapy (two from the imatinib arm and two from the IFN + AraC arm). Of the remaining 58 patients, 55 had 20 mL of peripheral blood collected for molecular analysis at more than one time point and were included in the study.

The researchers measured the levels of BCR-ABL transcript by real-time quantitative reverse transcriptase polymerase chain reaction and calculated the BCR-ABL/BCR percentage levels. The BCR-ABL protein is an activated tyrosine kinase that is causally associated with CML. These levels were significantly lower for the imatinib-treated patients at all points up to 18 months (P<0.0001). The median levels of BCR-ABL/BCR percentage for imatinib-treated patients continued to decrease and had not reached a plateau by 24 months.

A total of 24 patients on IFN + AraC crossed over to imatinib. In these cross-over patients, once imatinib commenced, the median BCR-ABL/BCR percentage was not different to those in patients on first-line imatinib therapy for the same number of months. Also, the estimated rate of complete cytogenetic response, defined as no Philadelphia chromosome positive metaphases at 18 months, was 76% for imatinib and 14.5% for IFN + AraC.

This study confirmed that first-line imatinib-treated patients with chronic-phase CML did better than those treated with first-line IFN + AraC, the authors conclude. However, those patients who crossed over from first-line IFN + AraC to imatinib early in the disease also had substantial reductions of BCR-ABL levels, they add.

This study was funded in part by grants from Novartis Pharmaceuticals, Australia.