Rapid BCR-ABL Reduction Is Predictive of Response in CML

A rapid reduction in BCR-ABL transcript levels and the halving time of those levels are predictive of better outcomes in patients with chronic myeloid leukemia (CML), according to a new retrospective analysis. The result was true regardless of which tyrosine kinase inhibitor (TKI) was administered as therapy.

“As more TKIs are now available, much attention has been paid to the identification of early prognostic markers during treatment,” wrote study authors led by Carmen Fava, MD, PhD, of the University of Turin in Italy. “Early response landmarks may identify patients at higher risk for transformation who would benefit from an early switch to second-line therapy.”

The researchers retrospectively analyzed 50 patients with CML treated with either imatinib, nilotinib, or dasatinib. The results were published in Clinical Lymphoma, Myeloma, and Leukemia.

In total, 34 patients (68%) had a BCR-ABL transcript of 10% or below at 3 months. Event-free survival (EFS) was better in those who achieved the greater BCR-ABL reduction; at 12 months, the probability of an event was 9% in those patients, compared with 50% in those with BCR-ABL > 10% at 3 months. By the median follow-up time of 61.8 months, the probabilities were 12% and 63%, respectively (P < .001).

No patient with a transcript level > 10% at 3 months achieved a major molecular response at 12 months, compared with 63% of those in the other group (P < .001).

The halving time threshold was found to be 17 days; this had a specificity of 75% and a sensitivity of 92.3% for predicting patients with molecular remission. No patient with a BCR-ABL transcript above 10% at 3 months had a halving time at or less than 17 days.

The patients with BCR-ABL at 10% or below at 3 months, as well as a halving time of 17 days or less, had significantly better EFS than other patients. The EFS at median follow-up for this group was 96%, compared with 60% for those with BCR-ABL ≤ 10% at 3 months but a halving time more than 17 days, and 27% for those with BCR-ABL > 10% at 3 months (P < .001).

“Irrespective of the TKI used, prognosis was significantly superior for patients with BCR-ABL ≤ 10% and halving time ≤ 17 days,” the authors concluded. “The prognostic role of early response is further confirmed by our data, which also support the role of halving time as a marker of favorable prognosis.”