Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: Follow-up of a phase 3 study

Neil P. Shah, François Guilhot, Jorge E. Cortes, Charles A. Schiffer, Philipp Le Coutre, Tim H. Brümmendorf, Hagop M. Kantarjian, Andreas Hochhaus, Philippe Rousselot, Hesham Mohamed, Diane Healey, Michael Cunningham, Giuseppe Saglio

Research output: Contribution to journalArticle

Abstract

We present long-term follow-up of a dasatinib phase 3 study of patients with imatinib-resistant/-intolerant chronic myeloid leukemia (CML). In the CA180-034 study, 670 patients with imatinib-resistant/-intolerant CML in chronic phase (CML-CP) received dasatinib 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. At 6 years, 188 (28%) of 670 patients remained on study treatment. Estimated 6-year protocol-defined progression-free survival (PFS) rates were 49%, 51%, 40%, and 47%, respectively, and estimated 6-year overall survival (OS) rates were 71%, 74%, 77%, and 70%, respectively (intent-to-treat population, including protocol-defined progression or death after discontinuation). Estimated 6-year rates of survival without transformation on study treatment were 76%, 80%, 83%, and 74%, respectively. Major molecular response was achieved in 43% (100 mg once daily) and 40% (all other arms) of patients by 6 years. Molecular and cytogenetic responses at 3 and 6 months were highly predictive of PFS and OS. Notably, estimated 6-year PFS rates based on ≤1%, >1% to 10%, and >10% BCR-ABL transcripts at 3months were 68%, 58%, and 26%, respectively. Most adverse events occurred by 2 years. Imatinib-resistant/-intolerant patients with CML-CP can experience long-term benefit with dasatinib therapy, particularly if achieving BCR-ABL ≤10% at 3 months. This study was registered at ClinicalTrials.gov: NCT00123474.

Original languageEnglish (US)
Pages (from-to)2317-2324
Number of pages8
JournalBlood
Volume123
Issue number15
DOIs
StatePublished - Apr 10 2014
Externally publishedYes

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

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia : Follow-up of a phase 3 study. / Shah, Neil P.; Guilhot, François; Cortes, Jorge E.; Schiffer, Charles A.; Le Coutre, Philipp; Brümmendorf, Tim H.; Kantarjian, Hagop M.; Hochhaus, Andreas; Rousselot, Philippe; Mohamed, Hesham; Healey, Diane; Cunningham, Michael; Saglio, Giuseppe.

In: Blood, Vol. 123, No. 15, 10.04.2014, p. 2317-2324.

Research output: Contribution to journalArticle

Shah, NP, Guilhot, F, Cortes, JE, Schiffer, CA, Le Coutre, P, Brümmendorf, TH, Kantarjian, HM, Hochhaus, A, Rousselot, P, Mohamed, H, Healey, D, Cunningham, M & Saglio, G 2014, 'Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: Follow-up of a phase 3 study', Blood, vol. 123, no. 15, pp. 2317-2324. https://doi.org/10.1182/blood-2013-10-532341
Shah, Neil P. ; Guilhot, François ; Cortes, Jorge E. ; Schiffer, Charles A. ; Le Coutre, Philipp ; Brümmendorf, Tim H. ; Kantarjian, Hagop M. ; Hochhaus, Andreas ; Rousselot, Philippe ; Mohamed, Hesham ; Healey, Diane ; Cunningham, Michael ; Saglio, Giuseppe. / Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia : Follow-up of a phase 3 study. In: Blood. 2014 ; Vol. 123, No. 15. pp. 2317-2324.
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abstract = "We present long-term follow-up of a dasatinib phase 3 study of patients with imatinib-resistant/-intolerant chronic myeloid leukemia (CML). In the CA180-034 study, 670 patients with imatinib-resistant/-intolerant CML in chronic phase (CML-CP) received dasatinib 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. At 6 years, 188 (28{\%}) of 670 patients remained on study treatment. Estimated 6-year protocol-defined progression-free survival (PFS) rates were 49{\%}, 51{\%}, 40{\%}, and 47{\%}, respectively, and estimated 6-year overall survival (OS) rates were 71{\%}, 74{\%}, 77{\%}, and 70{\%}, respectively (intent-to-treat population, including protocol-defined progression or death after discontinuation). Estimated 6-year rates of survival without transformation on study treatment were 76{\%}, 80{\%}, 83{\%}, and 74{\%}, respectively. Major molecular response was achieved in 43{\%} (100 mg once daily) and 40{\%} (all other arms) of patients by 6 years. Molecular and cytogenetic responses at 3 and 6 months were highly predictive of PFS and OS. Notably, estimated 6-year PFS rates based on ≤1{\%}, >1{\%} to 10{\%}, and >10{\%} BCR-ABL transcripts at 3months were 68{\%}, 58{\%}, and 26{\%}, respectively. Most adverse events occurred by 2 years. Imatinib-resistant/-intolerant patients with CML-CP can experience long-term benefit with dasatinib therapy, particularly if achieving BCR-ABL ≤10{\%} at 3 months. This study was registered at ClinicalTrials.gov: NCT00123474.",
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AU - Shah, Neil P.

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AU - Cortes, Jorge E.

AU - Schiffer, Charles A.

AU - Le Coutre, Philipp

AU - Brümmendorf, Tim H.

AU - Kantarjian, Hagop M.

AU - Hochhaus, Andreas

AU - Rousselot, Philippe

AU - Mohamed, Hesham

AU - Healey, Diane

AU - Cunningham, Michael

AU - Saglio, Giuseppe

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N2 - We present long-term follow-up of a dasatinib phase 3 study of patients with imatinib-resistant/-intolerant chronic myeloid leukemia (CML). In the CA180-034 study, 670 patients with imatinib-resistant/-intolerant CML in chronic phase (CML-CP) received dasatinib 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. At 6 years, 188 (28%) of 670 patients remained on study treatment. Estimated 6-year protocol-defined progression-free survival (PFS) rates were 49%, 51%, 40%, and 47%, respectively, and estimated 6-year overall survival (OS) rates were 71%, 74%, 77%, and 70%, respectively (intent-to-treat population, including protocol-defined progression or death after discontinuation). Estimated 6-year rates of survival without transformation on study treatment were 76%, 80%, 83%, and 74%, respectively. Major molecular response was achieved in 43% (100 mg once daily) and 40% (all other arms) of patients by 6 years. Molecular and cytogenetic responses at 3 and 6 months were highly predictive of PFS and OS. Notably, estimated 6-year PFS rates based on ≤1%, >1% to 10%, and >10% BCR-ABL transcripts at 3months were 68%, 58%, and 26%, respectively. Most adverse events occurred by 2 years. Imatinib-resistant/-intolerant patients with CML-CP can experience long-term benefit with dasatinib therapy, particularly if achieving BCR-ABL ≤10% at 3 months. This study was registered at ClinicalTrials.gov: NCT00123474.

AB - We present long-term follow-up of a dasatinib phase 3 study of patients with imatinib-resistant/-intolerant chronic myeloid leukemia (CML). In the CA180-034 study, 670 patients with imatinib-resistant/-intolerant CML in chronic phase (CML-CP) received dasatinib 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. At 6 years, 188 (28%) of 670 patients remained on study treatment. Estimated 6-year protocol-defined progression-free survival (PFS) rates were 49%, 51%, 40%, and 47%, respectively, and estimated 6-year overall survival (OS) rates were 71%, 74%, 77%, and 70%, respectively (intent-to-treat population, including protocol-defined progression or death after discontinuation). Estimated 6-year rates of survival without transformation on study treatment were 76%, 80%, 83%, and 74%, respectively. Major molecular response was achieved in 43% (100 mg once daily) and 40% (all other arms) of patients by 6 years. Molecular and cytogenetic responses at 3 and 6 months were highly predictive of PFS and OS. Notably, estimated 6-year PFS rates based on ≤1%, >1% to 10%, and >10% BCR-ABL transcripts at 3months were 68%, 58%, and 26%, respectively. Most adverse events occurred by 2 years. Imatinib-resistant/-intolerant patients with CML-CP can experience long-term benefit with dasatinib therapy, particularly if achieving BCR-ABL ≤10% at 3 months. This study was registered at ClinicalTrials.gov: NCT00123474.

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