Dasatinib early intervention after cytogenetic or hematologic resistance to imatinib in patients with chronic myeloid leukemia

Alfonso Quintás-Cardama, Jorge E. Cortes, Susan O'Brien, Farhad Ravandi, Gautam Borthakur, David Liu, Eric Bleickardt, Tai Tsang Chen, Hagop M. Kantarjian

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Although many patients with chronic myeloid leukemia (CML) respond well to imatinib therapy, a significant proportion loses their initial response. Loss of response on imatinib is often because of BCR-ABL mutations. Dasatinib is a 325-fold more potent inhibitor of Bcr-Abl than imatinib and has been associated with high rates of durable responses in patients with CML in chronic phase (CP) after imatinib failure. METHODS: To determine the optimal time for initiating dasatinib after loss of response on imatinib, data from dasatinib trials in CML-CP were analyzed. Patients were grouped according to whether they received early intervention with dasatinib (ie, after cytogenetic recurrence on imatinib), rather than after both cytogenetic and hematologic recurrence. RESULTS: Overall, 72% of patients who received dasatinib after loss of a major cytogenetic response (MCyR) on imatinib achieved a complete cytogenetic response (CCyR) compared with 42% of patients who were treated after loss of both MCyR and complete hematologic response (CHR). Event-free survival (EFS) also was higher after earlier dasatinib treatment (24-month EFS rates: 89% after loss of MCyR on imatinib vs 29% after loss of both MCyR and CHR). Among patients who were treated after loss of CHR on imatinib with no prior MCyR, 26% achieved a CCyR with dasatinib, and the 24-month EFS rate was 64%. In all 3 groups, CCyR rates were similar in patients with or without pre-existing BCR-ABL mutations. CONCLUSIONS: The results of the current study suggested that optimal outcomes are achieved when dasatinib is administered early after imatinib resistance.

Original languageEnglish (US)
Pages (from-to)2912-2921
Number of pages10
JournalCancer
Volume115
Issue number13
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
Disease-Free Survival
Leukemia, Myeloid, Chronic Phase
Survival Rate
Imatinib Mesylate
Dasatinib
Recurrence
Mutation
Therapeutics

Keywords

  • Antineoplastic drug resistance
  • Chronic myeloid leukemia
  • Dasatinib
  • Imatinib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Quintás-Cardama, A., Cortes, J. E., O'Brien, S., Ravandi, F., Borthakur, G., Liu, D., ... Kantarjian, H. M. (2009). Dasatinib early intervention after cytogenetic or hematologic resistance to imatinib in patients with chronic myeloid leukemia. Cancer, 115(13), 2912-2921. https://doi.org/10.1002/cncr.24325

Dasatinib early intervention after cytogenetic or hematologic resistance to imatinib in patients with chronic myeloid leukemia. / Quintás-Cardama, Alfonso; Cortes, Jorge E.; O'Brien, Susan; Ravandi, Farhad; Borthakur, Gautam; Liu, David; Bleickardt, Eric; Chen, Tai Tsang; Kantarjian, Hagop M.

In: Cancer, Vol. 115, No. 13, 01.07.2009, p. 2912-2921.

Research output: Contribution to journalArticle

Quintás-Cardama, A, Cortes, JE, O'Brien, S, Ravandi, F, Borthakur, G, Liu, D, Bleickardt, E, Chen, TT & Kantarjian, HM 2009, 'Dasatinib early intervention after cytogenetic or hematologic resistance to imatinib in patients with chronic myeloid leukemia', Cancer, vol. 115, no. 13, pp. 2912-2921. https://doi.org/10.1002/cncr.24325
Quintás-Cardama, Alfonso ; Cortes, Jorge E. ; O'Brien, Susan ; Ravandi, Farhad ; Borthakur, Gautam ; Liu, David ; Bleickardt, Eric ; Chen, Tai Tsang ; Kantarjian, Hagop M. / Dasatinib early intervention after cytogenetic or hematologic resistance to imatinib in patients with chronic myeloid leukemia. In: Cancer. 2009 ; Vol. 115, No. 13. pp. 2912-2921.
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abstract = "BACKGROUND: Although many patients with chronic myeloid leukemia (CML) respond well to imatinib therapy, a significant proportion loses their initial response. Loss of response on imatinib is often because of BCR-ABL mutations. Dasatinib is a 325-fold more potent inhibitor of Bcr-Abl than imatinib and has been associated with high rates of durable responses in patients with CML in chronic phase (CP) after imatinib failure. METHODS: To determine the optimal time for initiating dasatinib after loss of response on imatinib, data from dasatinib trials in CML-CP were analyzed. Patients were grouped according to whether they received early intervention with dasatinib (ie, after cytogenetic recurrence on imatinib), rather than after both cytogenetic and hematologic recurrence. RESULTS: Overall, 72{\%} of patients who received dasatinib after loss of a major cytogenetic response (MCyR) on imatinib achieved a complete cytogenetic response (CCyR) compared with 42{\%} of patients who were treated after loss of both MCyR and complete hematologic response (CHR). Event-free survival (EFS) also was higher after earlier dasatinib treatment (24-month EFS rates: 89{\%} after loss of MCyR on imatinib vs 29{\%} after loss of both MCyR and CHR). Among patients who were treated after loss of CHR on imatinib with no prior MCyR, 26{\%} achieved a CCyR with dasatinib, and the 24-month EFS rate was 64{\%}. In all 3 groups, CCyR rates were similar in patients with or without pre-existing BCR-ABL mutations. CONCLUSIONS: The results of the current study suggested that optimal outcomes are achieved when dasatinib is administered early after imatinib resistance.",
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AU - Quintás-Cardama, Alfonso

AU - Cortes, Jorge E.

AU - O'Brien, Susan

AU - Ravandi, Farhad

AU - Borthakur, Gautam

AU - Liu, David

AU - Bleickardt, Eric

AU - Chen, Tai Tsang

AU - Kantarjian, Hagop M.

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N2 - BACKGROUND: Although many patients with chronic myeloid leukemia (CML) respond well to imatinib therapy, a significant proportion loses their initial response. Loss of response on imatinib is often because of BCR-ABL mutations. Dasatinib is a 325-fold more potent inhibitor of Bcr-Abl than imatinib and has been associated with high rates of durable responses in patients with CML in chronic phase (CP) after imatinib failure. METHODS: To determine the optimal time for initiating dasatinib after loss of response on imatinib, data from dasatinib trials in CML-CP were analyzed. Patients were grouped according to whether they received early intervention with dasatinib (ie, after cytogenetic recurrence on imatinib), rather than after both cytogenetic and hematologic recurrence. RESULTS: Overall, 72% of patients who received dasatinib after loss of a major cytogenetic response (MCyR) on imatinib achieved a complete cytogenetic response (CCyR) compared with 42% of patients who were treated after loss of both MCyR and complete hematologic response (CHR). Event-free survival (EFS) also was higher after earlier dasatinib treatment (24-month EFS rates: 89% after loss of MCyR on imatinib vs 29% after loss of both MCyR and CHR). Among patients who were treated after loss of CHR on imatinib with no prior MCyR, 26% achieved a CCyR with dasatinib, and the 24-month EFS rate was 64%. In all 3 groups, CCyR rates were similar in patients with or without pre-existing BCR-ABL mutations. CONCLUSIONS: The results of the current study suggested that optimal outcomes are achieved when dasatinib is administered early after imatinib resistance.

AB - BACKGROUND: Although many patients with chronic myeloid leukemia (CML) respond well to imatinib therapy, a significant proportion loses their initial response. Loss of response on imatinib is often because of BCR-ABL mutations. Dasatinib is a 325-fold more potent inhibitor of Bcr-Abl than imatinib and has been associated with high rates of durable responses in patients with CML in chronic phase (CP) after imatinib failure. METHODS: To determine the optimal time for initiating dasatinib after loss of response on imatinib, data from dasatinib trials in CML-CP were analyzed. Patients were grouped according to whether they received early intervention with dasatinib (ie, after cytogenetic recurrence on imatinib), rather than after both cytogenetic and hematologic recurrence. RESULTS: Overall, 72% of patients who received dasatinib after loss of a major cytogenetic response (MCyR) on imatinib achieved a complete cytogenetic response (CCyR) compared with 42% of patients who were treated after loss of both MCyR and complete hematologic response (CHR). Event-free survival (EFS) also was higher after earlier dasatinib treatment (24-month EFS rates: 89% after loss of MCyR on imatinib vs 29% after loss of both MCyR and CHR). Among patients who were treated after loss of CHR on imatinib with no prior MCyR, 26% achieved a CCyR with dasatinib, and the 24-month EFS rate was 64%. In all 3 groups, CCyR rates were similar in patients with or without pre-existing BCR-ABL mutations. CONCLUSIONS: The results of the current study suggested that optimal outcomes are achieved when dasatinib is administered early after imatinib resistance.

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