Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy

Andreas Hochhaus, Hagop M. Kantarjian, Michele Baccarani, Jeffrey H. Lipton, Jane F. Apperley, Brian J. Druker, Thierry Facon, Stuart L. Goldberg, Francisco Cervantes, Dietger Niederwieser, Richard T. Silver, Richard M. Stone, Timothy Hughes, Martin C. Muller, Rana Ezzeddine, Athena M. Countouriotis, Neil P. Shah

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Abstract

Although imatinib induces marked responses in patients with chronic myeloid leukemia (CML), resistance is increasingly problematic, and treatment options for imatinib-resistant or -intolerant CML are limited. Dasatinib, a novel, highly potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, induced cytogenetic responses in a phase 1 study in imatinib-resistant or -intolerant CML and was well tolerated. Initial results are presented from a phase 2 study of 186 patients with imatinib-resistant or -intolerant chronic-phase CML (CML-CP) designed to further establish the efficacy and safety of dasatinib (70 mg twice daily). At 8-months' follow-up, dasatinib induced notable responses, with 90% and 52% of patients achieving complete hematologic and major cytogenetic responses (MCyR), respectively. Responses were long lasting: only 2% of patients achieving MCyRprogressed or died. Importantly, comparable responses were achieved by patients carrying BCR-ABL mutations conferring imatinib resistance. Dasatinib also induced molecular responses, reducing BCR-ABL/ABL transcript ratios from 66% at baseline to 2.6% at 9 months. Nonhematologic adverse events were generally mild to moderate, and most cytopenias were effectively managed with dose modifications. Cross-intolerance with imatinib was not evident. To conclude, dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients. This trial was registered at www.clinicaltrials.gov as CA180013.

LanguageEnglish
Pages2303-2309
Number of pages7
JournalBlood
Volume109
Issue number6
DOIs
Publication statusPublished - 15 Mar 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Hochhaus, A., Kantarjian, H. M., Baccarani, M., Lipton, J. H., Apperley, J. F., Druker, B. J., ... Shah, N. P. (2007). Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood, 109(6), 2303-2309. https://doi.org/10.1182/blood-2006-09-047266
Hochhaus, Andreas ; Kantarjian, Hagop M. ; Baccarani, Michele ; Lipton, Jeffrey H. ; Apperley, Jane F. ; Druker, Brian J. ; Facon, Thierry ; Goldberg, Stuart L. ; Cervantes, Francisco ; Niederwieser, Dietger ; Silver, Richard T. ; Stone, Richard M. ; Hughes, Timothy ; Muller, Martin C. ; Ezzeddine, Rana ; Countouriotis, Athena M. ; Shah, Neil P. / Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. In: Blood. 2007 ; Vol. 109, No. 6. pp. 2303-2309.
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abstract = "Although imatinib induces marked responses in patients with chronic myeloid leukemia (CML), resistance is increasingly problematic, and treatment options for imatinib-resistant or -intolerant CML are limited. Dasatinib, a novel, highly potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, induced cytogenetic responses in a phase 1 study in imatinib-resistant or -intolerant CML and was well tolerated. Initial results are presented from a phase 2 study of 186 patients with imatinib-resistant or -intolerant chronic-phase CML (CML-CP) designed to further establish the efficacy and safety of dasatinib (70 mg twice daily). At 8-months' follow-up, dasatinib induced notable responses, with 90{\%} and 52{\%} of patients achieving complete hematologic and major cytogenetic responses (MCyR), respectively. Responses were long lasting: only 2{\%} of patients achieving MCyRprogressed or died. Importantly, comparable responses were achieved by patients carrying BCR-ABL mutations conferring imatinib resistance. Dasatinib also induced molecular responses, reducing BCR-ABL/ABL transcript ratios from 66{\%} at baseline to 2.6{\%} at 9 months. Nonhematologic adverse events were generally mild to moderate, and most cytopenias were effectively managed with dose modifications. Cross-intolerance with imatinib was not evident. To conclude, dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients. This trial was registered at www.clinicaltrials.gov as CA180013.",
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Hochhaus, A, Kantarjian, HM, Baccarani, M, Lipton, JH, Apperley, JF, Druker, BJ, Facon, T, Goldberg, SL, Cervantes, F, Niederwieser, D, Silver, RT, Stone, RM, Hughes, T, Muller, MC, Ezzeddine, R, Countouriotis, AM & Shah, NP 2007, 'Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy', Blood, vol. 109, no. 6, pp. 2303-2309. https://doi.org/10.1182/blood-2006-09-047266

Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. / Hochhaus, Andreas; Kantarjian, Hagop M.; Baccarani, Michele; Lipton, Jeffrey H.; Apperley, Jane F.; Druker, Brian J.; Facon, Thierry; Goldberg, Stuart L.; Cervantes, Francisco; Niederwieser, Dietger; Silver, Richard T.; Stone, Richard M.; Hughes, Timothy; Muller, Martin C.; Ezzeddine, Rana; Countouriotis, Athena M.; Shah, Neil P.

In: Blood, Vol. 109, No. 6, 15.03.2007, p. 2303-2309.

Research output: Contribution to journalArticle

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AU - Kantarjian, Hagop M.

AU - Baccarani, Michele

AU - Lipton, Jeffrey H.

AU - Apperley, Jane F.

AU - Druker, Brian J.

AU - Facon, Thierry

AU - Goldberg, Stuart L.

AU - Cervantes, Francisco

AU - Niederwieser, Dietger

AU - Silver, Richard T.

AU - Stone, Richard M.

AU - Hughes, Timothy

AU - Muller, Martin C.

AU - Ezzeddine, Rana

AU - Countouriotis, Athena M.

AU - Shah, Neil P.

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N2 - Although imatinib induces marked responses in patients with chronic myeloid leukemia (CML), resistance is increasingly problematic, and treatment options for imatinib-resistant or -intolerant CML are limited. Dasatinib, a novel, highly potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, induced cytogenetic responses in a phase 1 study in imatinib-resistant or -intolerant CML and was well tolerated. Initial results are presented from a phase 2 study of 186 patients with imatinib-resistant or -intolerant chronic-phase CML (CML-CP) designed to further establish the efficacy and safety of dasatinib (70 mg twice daily). At 8-months' follow-up, dasatinib induced notable responses, with 90% and 52% of patients achieving complete hematologic and major cytogenetic responses (MCyR), respectively. Responses were long lasting: only 2% of patients achieving MCyRprogressed or died. Importantly, comparable responses were achieved by patients carrying BCR-ABL mutations conferring imatinib resistance. Dasatinib also induced molecular responses, reducing BCR-ABL/ABL transcript ratios from 66% at baseline to 2.6% at 9 months. Nonhematologic adverse events were generally mild to moderate, and most cytopenias were effectively managed with dose modifications. Cross-intolerance with imatinib was not evident. To conclude, dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients. This trial was registered at www.clinicaltrials.gov as CA180013.

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