Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase

J. Cortes, D. W. Kim, E. Raffoux, G. Martinelli, E. Ritchie, L. Roy, S. Coutre, S. Corm, N. Hamerschlak, J. L. Tang, A. Hochhaus, H. J. Khoury, T. H. Brümmendorf, M. Michallet, G. Rege-Cambrin, C. Gambacorti-Passerini, J. P. Radich, T. Ernst, C. Zhu, J. M.A. Van TornoutM. Talpaz

Research output: Contribution to journalArticle

Abstract

Dasatinib is an inhibitor of BCR-ABL and SRC-family kinases for patients with imatinib-resistant or -intolerant chronic myelogenous leukemia (CML). In this international phase II trial, dasatinib was administered orally (70mg twice daily) to patients with myeloid blast phase (MBP, n=109) or lymphoid blast phase (LBP, n=48) CML. After a minimum follow-up of 12 months (range 0.03-20.7 months), major hematologic responses were induced in 34% (MBP-CML) and 35% (LBP-CML) of patients. Major cytogenetic responses were attained in 33% (MBP-CML) and 52% (LBP-CML) of patients and complete cytogenetic responses were attained in 26 and 46%, respectively. Median progression-free survival was 6.7 (MBP-CML) and 3.0 (LBP-CML) months. Median overall survival was 11.8 (MBP-CML) and 5.3 (LBP-CML) months. Overall, dasatinib had acceptable tolerability. Fluid retention events were more frequent in the MBP-CML than the LBP-CML cohort: pleural effusion occurred in 36 and 13% (all grades) and 15 and 6% (grades 3/4), respectively. Other non-hematologic side effects were primarily grade 1/2; grade 3/4 events were recorded in ≤6% of patients, except febrile neutropenia (15%). Cytopenias were noted in the majority of patients, and were manageable with dose interruptions/reductions. Dasatinib is associated with a promising rate of response in this high-risk population.

Original languageEnglish (US)
Pages (from-to)2176-2183
Number of pages8
JournalLeukemia
Volume22
Issue number12
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

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Blast Crisis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Safety
Cytogenetics
Imatinib Mesylate
Dasatinib
Febrile Neutropenia
Pleural Effusion
Disease-Free Survival

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase. / Cortes, J.; Kim, D. W.; Raffoux, E.; Martinelli, G.; Ritchie, E.; Roy, L.; Coutre, S.; Corm, S.; Hamerschlak, N.; Tang, J. L.; Hochhaus, A.; Khoury, H. J.; Brümmendorf, T. H.; Michallet, M.; Rege-Cambrin, G.; Gambacorti-Passerini, C.; Radich, J. P.; Ernst, T.; Zhu, C.; Van Tornout, J. M.A.; Talpaz, M.

In: Leukemia, Vol. 22, No. 12, 01.01.2008, p. 2176-2183.

Research output: Contribution to journalArticle

Cortes, J, Kim, DW, Raffoux, E, Martinelli, G, Ritchie, E, Roy, L, Coutre, S, Corm, S, Hamerschlak, N, Tang, JL, Hochhaus, A, Khoury, HJ, Brümmendorf, TH, Michallet, M, Rege-Cambrin, G, Gambacorti-Passerini, C, Radich, JP, Ernst, T, Zhu, C, Van Tornout, JMA & Talpaz, M 2008, 'Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase', Leukemia, vol. 22, no. 12, pp. 2176-2183. https://doi.org/10.1038/leu.2008.221
Cortes, J. ; Kim, D. W. ; Raffoux, E. ; Martinelli, G. ; Ritchie, E. ; Roy, L. ; Coutre, S. ; Corm, S. ; Hamerschlak, N. ; Tang, J. L. ; Hochhaus, A. ; Khoury, H. J. ; Brümmendorf, T. H. ; Michallet, M. ; Rege-Cambrin, G. ; Gambacorti-Passerini, C. ; Radich, J. P. ; Ernst, T. ; Zhu, C. ; Van Tornout, J. M.A. ; Talpaz, M. / Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase. In: Leukemia. 2008 ; Vol. 22, No. 12. pp. 2176-2183.
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AU - Raffoux, E.

AU - Martinelli, G.

AU - Ritchie, E.

AU - Roy, L.

AU - Coutre, S.

AU - Corm, S.

AU - Hamerschlak, N.

AU - Tang, J. L.

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AU - Khoury, H. J.

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AU - Radich, J. P.

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N2 - Dasatinib is an inhibitor of BCR-ABL and SRC-family kinases for patients with imatinib-resistant or -intolerant chronic myelogenous leukemia (CML). In this international phase II trial, dasatinib was administered orally (70mg twice daily) to patients with myeloid blast phase (MBP, n=109) or lymphoid blast phase (LBP, n=48) CML. After a minimum follow-up of 12 months (range 0.03-20.7 months), major hematologic responses were induced in 34% (MBP-CML) and 35% (LBP-CML) of patients. Major cytogenetic responses were attained in 33% (MBP-CML) and 52% (LBP-CML) of patients and complete cytogenetic responses were attained in 26 and 46%, respectively. Median progression-free survival was 6.7 (MBP-CML) and 3.0 (LBP-CML) months. Median overall survival was 11.8 (MBP-CML) and 5.3 (LBP-CML) months. Overall, dasatinib had acceptable tolerability. Fluid retention events were more frequent in the MBP-CML than the LBP-CML cohort: pleural effusion occurred in 36 and 13% (all grades) and 15 and 6% (grades 3/4), respectively. Other non-hematologic side effects were primarily grade 1/2; grade 3/4 events were recorded in ≤6% of patients, except febrile neutropenia (15%). Cytopenias were noted in the majority of patients, and were manageable with dose interruptions/reductions. Dasatinib is associated with a promising rate of response in this high-risk population.

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