Prognosis for patients with CML and >10% BCR-ABL1after 3 months of imatinib depends on the rate of BCR-ABL1decline

In chronic myeloid leukemia (CML) patients, a breakpoint cluster region–Abelson (BCR-ABL1) value >10% at 3 months of therapy is statistically associated with poorer outcome, yet many of these patients still achieve satisfactory outcomes. We investigated 528 first-line imatinib-treated patients to determine whether patients with the poorest outcome can be better discriminated at 3 months. All outcomes were significantly superior for the 410 patients with BCR-ABL1≤10% at 3 months (P< .001). However, the poorest outcomes among the 95 evaluable patients with BCR-ABL1>10% at 3 months were identified by the rate of BCR-ABL1decline from baseline, assessed by estimating the number of days over which BCR-ABL1halved. Patients with BCR-ABL1halving time <76 days (n = 74) had significantly superior outcomes compared with patients whose BCR-ABL1values did not halve by 76 days (n = 21; 4-year overall survival, 95% vs 58%, P= .0002; progression-free survival, 92% vs 63%, P= .008; failure-free survival, 59% vs 6%, P< .0001; and major molecular response, 54% vs 5%, P= .008). By multivariate analysis, the halving time was an independent predictor of outcome in this poor risk group. Our study highlighted that the rate of BCR-ABL1decline may be a critical prognostic discriminator of the patients with very poor outcome among those >10% at 3 months. The International Randomized IFN vs STI571 (IRIS) trial was registered at http://www.clinicaltrials.govas #NCT00006343. The Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) trial was registered at http://www.clinicaltrials.govas #NCT00124748. The Therapeutic Intensification in DE-novo Leukaemia (TIDEL) I trial was registered at http://www.ANZCTR.org.auas #ACTRN12607000614493. The TIDEL II trial was registered at http://www.ANZCTR.org.auas #ACTRN12607000325404.