Baseline kinetics of breakpoint cluster region (BCR)-ABL proto-oncogene 1 (ABL1) and decline over time in patients with chronic myeloid leukemia (CML) was associated with long-term remission status. These findings were published in the journal Blood.
Long-term treatment-free remission (TFR) is becoming the goal of therapy for patients with CML, and to achieve this, strategies that sustain TFR are needed. Therefore, researchers conducted this study to identify key determinants of sustained treatment-free remission.
Researchers identified 115 patients who were in treatment-free remission from CML for at least 12 months following tyrosine kinase inhibitor (TKI) treatment at university hospitals in Southern Australia between 2008 and 2019 were retrospectively assessed for BCR–ABL1 kinetics and long-term remission status.
The study population was 53.0% men, median age 60.9 years (range, 33.4 to 89.8) at treatment-free remission, and had been treated with a TKI for a median of 7.0 years (range, 3.0 to 17.6).
At 12 months, 55% remained in remission and loss of major molecular response triggered restart of TKI therapy for 45 patients.
Patients who sustained and lost their remission status differed by BCR–ABL1 halving time (median, 10.1 vs 21.7 days; P <.001). All patients who had a BCR–ABL1 halving time of more than 21.85 days experienced molecular relapse.
At 3 months, patients with a BCR–ABL1 fold-reduction greater than 543.4 had the highest probability for maintaining their remission status compared with patients who had a fold-reduction between 125.5 and 543.4 (P =.017), between 29.8 and 125.4 (P =.016), or less than 29.8 (P <.001).
Significant predictors of relapse were the e13a2 transcript (hazard ratio [HR], 2.49; 95% CI, 1.39-4.46; P =.002) and duration of TKI therapy (HR, 2.61; 95% CI, 1.05-6.09; P =.03).
This study may have been limited by the choice of control gene in the BCR–ABL1 halving assays.
The study authors concluded initial decline of BCR–ABL1 associated with sustained treatment-free remission among patients with CML.
Disclosure: Multiple authors declared affiliations with and received funding from the pharmaceutical industry. Please refer to the original article for a full list of disclosures.
Shanmuganathan N, Pagani I S, Ross D M, et al. Early BCR-ABL1 kinetics are predictive of subsequent achievement of treatment-free remission in chronic myeloid leukemia. Blood. 2021;137(9):1196-1207. doi:10.1182/blood.2020005514.