Early BCR-ABL Reduction Predictive of Response in Newly Diagnosed CML

For patients with newly diagnosed chronic myeloid leukemia (CML), an early BCR-ABL reduction is predictive of better event-free survival regardless of the tyrosine kinase inhibitor (TKI) used, a study published in the journal Clinical Lymphoma, Myeloma & Leukemia has shown.¹

Early molecular response is strongly predictive in CML and it has recently been determined that halving time has prognostic value, as well. Therefore, researchers sought to evaluate the prognostic significance of the 3 months time-point in newly diagnosed patients with CML receiving a TKI.

For the study, researchers retrospectively analyzed BCR-ABL transcript data at different time-points, event data, and survival data from 50 patients in chronic phase. Patients were treated with imatinib, nilotinib, or dasatinib, and had undergone molecular evaluation at 3 months.

Results showed that 68% of patients had a BCR-ABL transcript of 10% or less at 3 months. Researchers found that 63% of patients in the > 10% group experienced an event compared with 12% in the ≤ 10% group by the median time of follow-up (P < .001).

The study further demonstrated that a halving of 17 days or less was associated with improved event-free survival, and no patients with a transcript > 10% at 3 months had a halving time ≤ 17 days.

Patients with BCR-ABL ≤ 10% and a halving time ≤ 17 days had a significantly improved event-free survival compared with patients with BCR-ABL ≤ 10% and halving time > 17 days and patients with BCR-ABL > 10% (P < .001).

The findings ultimately suggest that the use of ABL as a control gene is reliable for the determination of the halving time in the clinical setting, thus underscoring the importance of measuring the BCR-ABL transcript at the time of diagnosis.

Reference

1. Fava C, Rege-Cambrin G, Dogliotti I, et al. Early BCR-ABL reduction is predictive of better event free survival in chronic myeloid leukemia newly diagnosed patients treated with any tyrosine kinase inhibitors [published online ahead of print April 1, 2016]. Clin Lymphoma Myeloma Leuk. doi:  10.1016/j.clml.2016.03.008.