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 Yeung, W Parker, N Roberts, L Purins, J Braley, H Altamura, A Yeoman, J Georgievski, B Jamison, S Phillis, Z Donaldson, Mary Leong, L Fletcher, J. Seymour, A Grigg, David Ross, Timothy Hughes

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    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 - 2014

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    Branford, S., Yeung, D., Parker, W., Roberts, N., Purins, L., Braley, J., Altamura, H., Yeoman, A., Georgievski, J., Jamison, B., Phillis, S., Donaldson, Z., Leong, M., Fletcher, L., Seymour, J., Grigg, A., Ross, D., & Hughes, T. (2014). Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline. Blood, 124(4), 511-518. https://doi.org/10.1182/blood-2014-03-566323