Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline

Susan Branford, David T. Yeung, Wendy T. Parker, Nicola D. Roberts, Leanne Purins, Jodi A. Braley, Haley K. Altamura, Alexandra L. Yeoman, Jasmina Georgievski, Bronte A. Jamison, Stuart Phillis, Zoe Donaldson, Mary Leong, Linda Fletcher, John F. Seymour, Andrew P. Grigg, David M. Ross, Timothy P. Hughes

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135 Citations (Scopus)

Abstract

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, yetmanyof these patients still achieve satisfactory outcomes. We in vestigated 528 first-lineimatinib-treated patients to determine whether patients with the poorestoutcome 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-ABL1 decline from baseline, assessed by estimating the number of days over which BCR-ABL1 halved. Patients with BCR-ABL1 halving time <76 days (n = 74) had significantly superior outcomes compared with patients whose BCR-ABL1 values 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-ABL1 decline may be a critical prognostic discriminator of the patients with very poor outcome among those >10% at 3 months. The International Randomized IFNvs STI571 (IRIS) trialwas registered at http://www.clinicaltrials.gov as #NCT00006343. The Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) trial was registered at http://www. clinicaltrials.gov as #NCT00124748. The Therapeutic Intensification in DE-novo Leukaemia (TIDEL) I trial was registered at http://www.ANZCTR.org.au as #ACTRN12607000614493. The TIDEL II trial was registered at http://www.ANZCTR. org.au as #ACTRN12607000325404.

Original languageEnglish
Pages (from-to)511-518
Number of pages8
JournalBlood
Volume124
Issue number4
DOIs
Publication statusPublished - 24 Jul 2014

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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