Tyrosine kinase inhibitors in acute and chronic leukemias

Maro Ohanian, Jorge Cortes, Hagop Kantarjian, Elias Jabbour

Research output: Contribution to journalReview article

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 languageEnglish (US)
Pages (from-to)927-938
Number of pages12
JournalExpert Opinion on Pharmacotherapy
Volume13
Issue number7
DOIs
StatePublished - May 1 2012
Externally publishedYes

Fingerprint

Protein-Tyrosine Kinases
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Acute Myeloid Leukemia
Mutation
Philadelphia Chromosome
Investigational Therapies
Expert Testimony
Therapeutics
Drug-Related Side Effects and Adverse Reactions
Drug Interactions
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Comorbidity
Research

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 journalReview article

Ohanian, Maro ; Cortes, Jorge ; Kantarjian, Hagop ; Jabbour, Elias. / Tyrosine kinase inhibitors in acute and chronic leukemias. In: Expert Opinion on Pharmacotherapy. 2012 ; Vol. 13, No. 7. pp. 927-938.
@article{eb80000fa2dd4ef4bf604912830a293e,
title = "Tyrosine kinase inhibitors in acute and chronic leukemias",
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.",
keywords = "Acute myelogenous leukemia, Chronic myelogenous leukemia, Philadelphia-chromosome-positive acute lymphoblastic leukemia, Tyrosine kinase inhibitors",
author = "Maro Ohanian and Jorge Cortes and Hagop Kantarjian and Elias Jabbour",
year = "2012",
month = "5",
day = "1",
doi = "10.1517/14656566.2012.672974",
language = "English (US)",
volume = "13",
pages = "927--938",
journal = "Expert Opinion on Pharmacotherapy",
issn = "1465-6566",
publisher = "Informa Healthcare",
number = "7",

}

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

UR - http://www.scopus.com/inward/record.url?scp=84860174035&partnerID=8YFLogxK

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 -