Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia: Results with four tyrosine kinase inhibitor modalities

Preetesh Jain, Hagop Kantarjian, Aziz Nazha, Susan O’Brien, Elias Jabbour, Carlos Guillermo Romo, Sherry Pierce, Marylou Cardenas-Turanzas, Srdan Verstovsek, Gautam Borthakur, Farhad Ravandi, Alfonso Quintás-Cardama, Jorge Cortes

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

Early responses to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML)-chronic phase (CP) are associated with improved outcome. We analyzed the impact of such a response on outcomes among patients treated with 4 TKI modalities as frontline therapy in CML-CP. A total of 483 patients who received 400 or 800 mg imatinib, nilotinib, or dasatinib were analyzed. The median follow-up was 72 mo. Landmark analysis at 3 mo by molecular response showed that the cumulative proportions of 3-y event-free survival (EFS) for 3-mo BCR-ABL levels was 95% for those with £1%, 98% for >1% to 10%, and 61% for those with >10% (P 5 .001). The corresponding values by cytogenetic responses were 97% if Ph1 5 0%, 89% if Ph1 5 1% to 35%, and 81% if Ph1 >35% (P 5 .001). Cytogenetic response at 3 mo significantly discriminated for 3-y overall survival (OS): 98%, 96%, and 92%, respectively (P 5 .01). In multivariate analysis, young patients, high Sokal index, and treatment with imatinib 400 significantly predicted for poor (>35%) cytogenetic response at 3 mo. Early responses are predictive for EFS and failure-free survival and to a lesser extent OS, regardless of the treatment modality, although therapies other than standard-dose imatinib result in higher rates of deep early responses. This trial was registered at www.clinicaltrials.gov as ID01-151 NCT00038649, ID01-015 NCT00048672, DM00-163 NCT00333840, ID02-534 NCT00050531, 2005-0422 NCT00254423, and 2005-0048 NCT00129740.

Original languageEnglish (US)
Pages (from-to)4867-4874
Number of pages8
JournalBlood
Volume121
Issue number24
DOIs
StatePublished - Jun 13 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Jain, P., Kantarjian, H., Nazha, A., O’Brien, S., Jabbour, E., Romo, C. G., Pierce, S., Cardenas-Turanzas, M., Verstovsek, S., Borthakur, G., Ravandi, F., Quintás-Cardama, A., & Cortes, J. (2013). Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia: Results with four tyrosine kinase inhibitor modalities. Blood, 121(24), 4867-4874. https://doi.org/10.1182/blood-2013-03-490128