Abstract
Introduction: Since the initial approval of imatinib much has been learned about its resistance mechanisms, and efforts have continued to improve upon BCR-ABL tyrosine kinase inhibitor therapy. Targeted therapy with TKIs has continued to be an area of active research and development in the care of acute and chronic leukemia patients. Areas covered: This article reviews current approved and investigational TKI treatments for chronic myelogenous leukemia (CML), Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph + ALL) and acute myelogenous leukemia (AML). Expert opinion: There are now more potent BCR-ABL TKIs approved, which allow for additional options when determining front-line and second-line CML and Ph + ALL treatments. The T315I mutation is an ever-present challenge. Ponatinib, a pan BCR-ABL TKI, while still under investigation, is very hopeful with its ability to overcome T315I mutations in resistant CML and Ph + ALL patients. Because nilotinib and dasatinib have not been directly compared, at present we recommend selecting one or the other based on the side-effect profile, drug interactions, patient comorbidities, and mutational status. FLT-3 inhibition is of particular interest in AML patients with FLT-3 internal tandem duplication mutations; this type of targeted therapy continues to be studied.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 927-938 |
| Number of pages | 12 |
| Journal | Expert Opinion on Pharmacotherapy |
| Volume | 13 |
| Issue number | 7 |
| DOIs | |
| State | Published - May 1 2012 |
| Externally published | Yes |
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Keywords
- Acute myelogenous leukemia
- Chronic myelogenous leukemia
- Philadelphia-chromosome-positive acute lymphoblastic leukemia
- Tyrosine kinase inhibitors
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
Cite this
Tyrosine kinase inhibitors in acute and chronic leukemias. / Ohanian, Maro; Cortes, Jorge; Kantarjian, Hagop; Jabbour, Elias.
In: Expert Opinion on Pharmacotherapy, Vol. 13, No. 7, 01.05.2012, p. 927-938.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Tyrosine kinase inhibitors in acute and chronic leukemias
AU - Ohanian, Maro
AU - Cortes, Jorge
AU - Kantarjian, Hagop
AU - Jabbour, Elias
PY - 2012/5/1
Y1 - 2012/5/1
N2 - Introduction: Since the initial approval of imatinib much has been learned about its resistance mechanisms, and efforts have continued to improve upon BCR-ABL tyrosine kinase inhibitor therapy. Targeted therapy with TKIs has continued to be an area of active research and development in the care of acute and chronic leukemia patients. Areas covered: This article reviews current approved and investigational TKI treatments for chronic myelogenous leukemia (CML), Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph + ALL) and acute myelogenous leukemia (AML). Expert opinion: There are now more potent BCR-ABL TKIs approved, which allow for additional options when determining front-line and second-line CML and Ph + ALL treatments. The T315I mutation is an ever-present challenge. Ponatinib, a pan BCR-ABL TKI, while still under investigation, is very hopeful with its ability to overcome T315I mutations in resistant CML and Ph + ALL patients. Because nilotinib and dasatinib have not been directly compared, at present we recommend selecting one or the other based on the side-effect profile, drug interactions, patient comorbidities, and mutational status. FLT-3 inhibition is of particular interest in AML patients with FLT-3 internal tandem duplication mutations; this type of targeted therapy continues to be studied.
AB - Introduction: Since the initial approval of imatinib much has been learned about its resistance mechanisms, and efforts have continued to improve upon BCR-ABL tyrosine kinase inhibitor therapy. Targeted therapy with TKIs has continued to be an area of active research and development in the care of acute and chronic leukemia patients. Areas covered: This article reviews current approved and investigational TKI treatments for chronic myelogenous leukemia (CML), Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph + ALL) and acute myelogenous leukemia (AML). Expert opinion: There are now more potent BCR-ABL TKIs approved, which allow for additional options when determining front-line and second-line CML and Ph + ALL treatments. The T315I mutation is an ever-present challenge. Ponatinib, a pan BCR-ABL TKI, while still under investigation, is very hopeful with its ability to overcome T315I mutations in resistant CML and Ph + ALL patients. Because nilotinib and dasatinib have not been directly compared, at present we recommend selecting one or the other based on the side-effect profile, drug interactions, patient comorbidities, and mutational status. FLT-3 inhibition is of particular interest in AML patients with FLT-3 internal tandem duplication mutations; this type of targeted therapy continues to be studied.
KW - Acute myelogenous leukemia
KW - Chronic myelogenous leukemia
KW - Philadelphia-chromosome-positive acute lymphoblastic leukemia
KW - Tyrosine kinase inhibitors
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UR - http://www.scopus.com/inward/citedby.url?scp=84860174035&partnerID=8YFLogxK
U2 - 10.1517/14656566.2012.672974
DO - 10.1517/14656566.2012.672974
M3 - Review article
C2 - 22519766
AN - SCOPUS:84860174035
VL - 13
SP - 927
EP - 938
JO - Expert Opinion on Pharmacotherapy
JF - Expert Opinion on Pharmacotherapy
SN - 1465-6566
IS - 7
ER -