Suboptimal Rate of Initial BRC-ABL1 Decline on Imatinib Signals Change in Inhibitor Warranted

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Patients with high Sokal risk treated with imatinib have a higher rate of treatment failure and poorer molecular response.
Patients with high Sokal risk treated with imatinib have a higher rate of treatment failure and poorer molecular response.

SAN FRANCISCO—Patients with high Sokal risk treated with imatinib have a higher rate of treatment failure and poorer molecular response, according to study results (Abstract 816) presented at the 56th American Society of Hematology Annual Meeting and Exposition.

“However, our data suggest their prognosis can be refined by taking into account the kinetics of BCR-ABL decline after only 1 month of treatment,” said Susan Branford, PhD, of the Centre for Cancer Biology, SA Pathology, and Schools of Medicine, Molecular and Biomedical Science, and Pharmacy and Medical Science in Adelaide, Australia.

“A rapid initial decline defined a subgroup of high Sokal risk patients with outcomes equivalent to those of low Sokal risk patients,” she added. “Frequent molecular monitoring in the critical first months of treatment could enhance outcome prediction and limit the indication for a change of treatment.”

The goal of the study was to determine whether baseline factors such as age, gender, Sokal risk and imatinib starting dose (400, 600, or 800 mg) and the BCR-ABL halving time at 1 month following treatment initiation with imatinib have predictive significance.

Dr. Branford and colleagues evaluated 528 patients treated first-line with imatinib who had received a median of 45 months of therapy. Of these patients, 453 of 470 who had molecular assessment performed prior to imatinib and at 1 months had a Sokal score available and were included in the analysis.

At 1 month of imatinib treatment, median BCR-ABL halving time was 17 days (quartiles 11, 29), with an initial rapid decline associated with significantly superior rates of major molecular response by 12 months, MR4.5, and failure-free survival (FFS) by 4 years compared with longer halving times of greater than 11 days, the lowest quartile.

When the patients were divided into 2 groups according to their 1 month halving time, for those whose time was 11 days or fewer, outcomes were significantly improved. Responses equated to those of patients with low Sokal risk, Dr. Branford said. High Sokal risk patients with rapid initial BCR-ABL decline also had a lower probability of BCR-ABL greater than 10% at 3 months, considered a warning of treatment failure.

“Our study may have revealed a difference in the underlying biology between patients with a Sokal risk group,” Dr. Branfordd said. “For imatinib-treated patients, an initial rapid rate of BCR-ABL1 decline could be reassuring for patients with intermediate or high Sokal risk,” while a “more potent TKI [tyrosine kinase inhibitor] could be reserved for those with a suboptimal rate of initial BRC-ABL1 decline.

  1. Branford, Susan, PhD, et al. "816 The Adverse Effect of High Sokal Risk for First Line Imatinib Treated Patients Is Overcome By a Rapid Rate of BCR-ABL Decline Measured As Early As 1 Month of Treatment." ASH 2014. Oral Presentation. December 9, 2014.

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