Measurement of molecular response to treatment indicates that imatinib is superior to interferon alfa plus cytarabine as initial therapy for Philadelphia chromosome-positive chronic myeloid leukemia, according to an article in the October 9th issue of the New England Journal of Medicine.

In the International Randomized Study of Interferon versus STI571 (IRIS), researchers randomized 1,106 patients with newly diagnosed chronic myeloid leukemia who were positive for the Philadelphia chromosome to imatinib or interferon alfa plus cytarabine. Patients who achieved complete cytogenetic remission were followed with serial blood testing for BCR-ABL transcripts, which produce the abnormal protein that drives proliferation of leukemic cells.

Molecular testing was done with quantitative polymerase-chain-reaction assay, and results were expressed relative to median blood levels in 30 peers with untreated disease in the chronic phase.

Patients in complete cytogenetic remission at 12 months whose transcript levels had decreased by at least 1,000 (or 3 log) had a 100-percent probability of remaining free of disease progression for the next 12 months compared with 95-percent probability with a reduction of less than 1,000. Patients who did not maintain complete cytogenetic remission through the first 12 months had an 85-percent probability of remaining progression-free for the next 12 months.

When imatinib and interferon plus cytarabine were compared in terms of complete cytogenetic remission, researchers found that 68 percent of patients in the imatinib group were in remission at 12 months compared with 7 percent for the combination therapy patients.

When the predictive value of molecular response was analyzed for patients in each treatment arm, researchers found that 57 percent of patients in the imatinib group had a decrease of at least 1,000 at 12 months compared with only 24 percent in the interferon plus cytarabine group.

Based on their findings, the authors propose that a 1000-fold reduction should be defined as a “major molecular response” and suggest that monitoring of BCR-ABL level may be a predictive marker for long-term outcome.