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

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
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Cytogenetics
Leukemia, Myeloid, Chronic Phase
Disease-Free Survival
Survival
Therapeutics
Multivariate Analysis
Imatinib Mesylate

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia : Results with four tyrosine kinase inhibitor modalities. / Jain, Preetesh; Kantarjian, Hagop; Nazha, Aziz; O’Brien, Susan; Jabbour, Elias; Romo, Carlos Guillermo; Pierce, Sherry; Cardenas-Turanzas, Marylou; Verstovsek, Srdan; Borthakur, Gautam; Ravandi, Farhad; Quintás-Cardama, Alfonso; Cortes, Jorge.

In: Blood, Vol. 121, No. 24, 13.06.2013, p. 4867-4874.

Research output: Contribution to journalArticle

Jain, P, Kantarjian, H, Nazha, A, O’Brien, S, Jabbour, E, Romo, CG, 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, vol. 121, no. 24, pp. 4867-4874. https://doi.org/10.1182/blood-2013-03-490128
Jain, Preetesh ; Kantarjian, Hagop ; Nazha, Aziz ; O’Brien, Susan ; Jabbour, Elias ; Romo, Carlos Guillermo ; Pierce, Sherry ; Cardenas-Turanzas, Marylou ; Verstovsek, Srdan ; Borthakur, Gautam ; Ravandi, Farhad ; Quintás-Cardama, Alfonso ; Cortes, Jorge. / Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia : Results with four tyrosine kinase inhibitor modalities. In: Blood. 2013 ; Vol. 121, No. 24. pp. 4867-4874.
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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.",
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AU - O’Brien, Susan

AU - Jabbour, Elias

AU - Romo, Carlos Guillermo

AU - Pierce, Sherry

AU - Cardenas-Turanzas, Marylou

AU - Verstovsek, Srdan

AU - Borthakur, Gautam

AU - Ravandi, Farhad

AU - Quintás-Cardama, Alfonso

AU - Cortes, Jorge

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