BFORE: 3-month BCR-ABL1 transcript levels may predict major molecular response in CML
In the first-line treatment of Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML), patients presenting BCR-ABL1 transcript levels ≤10 percent at 3 months are more likely to achieve major molecular response (MMR) at 12 months with faster response rate compared with those who have transcript levels >10 percent, according to ≥12 months of follow-up data from the BFORE* trial.
The ongoing, multinational phase III trial has randomized adult Ph+ CML patients to receive either bosutinib 400 mg (n=268) or imatinib 400 mg (n=268) once daily. Among evaluable patients at 3 months, more patients in the bosutinib than in the imatinib arm had BCR-ABL1 transcripts ≤10 percent (80.6 percent of 248 vs 60.5 percent of 253; p<0.0001). [ASH 2017, abstract 1618]
Factors predicting longer time to BCR-ABL1 transcript levels ≤10 percent included Sokal risk group (bosutinib: high vs low risk; imatinib: high vs low and intermediate vs low risk) and actual dose received (bosutinib: ≤200 vs 400 mg; imatinib: 300 vs 400 mg).
Of note, patients with 3-month transcripts ≤10 vs >10 percent had higher MMR rate at 12 months with bosutinib (58.5 vs 14.6 percent; p<0.0001) and with imatinib (54.2 vs 14.0 percent; p<0.0001). Cumulative MMR rates were likewise higher in patients achieving transcripts ≤10 percent with bosutinib (69.0 vs 25 percent; p<0.0001) and with imatinib (65.4 vs 30.0 percent; p<0.0001).
In the overall population, BCR-ABL1 transcripts ≤10 percent (vs >10 percent or not evaluable) at 3 months significantly predicted time to MMR in both treatment arms (bosutinib: hazard ratio [HR], 3.743; p<0.001; imatinib: HR, 2.906; p<0.001).
Among other covariates examined, Sokal risk group (high vs low risk) and actual dose received (500 vs 400 mg) emerged as predictors of longer time to MMR with bosutinib.
“These findings suggest that BCR-ABL1 transcript levels at 3 months may be a predictor of MMR to first-line treatment with bosutinib or imatinib in newly diagnosed patients with Ph+ [chronic phase] CML,” the authors said, adding that the data are in line with previous studies demonstrating the utility of BCR-ABL1 transcripts as predictors of response in patients with CML. [N Engl J Med 2006;355:2408-17; Leuk Res 2016;48:20-25]
CML is caused by reciprocal chromosomal t(9;22) translocation, resulting in formation of the Philadelphia chromosome and expression of the BCR-ABL1 fusion gene. Bosutinib, a potent SRC/ABL tyrosine kinase inhibitor, is approved for treatment of PH+ CP CML in adults resistant or intolerant to prior therapy.
*Bosutinib trial in first-line chronic myelogenous leukemia treatment