Chronic myeloid leukemia in the tyrosine kinase inhibitor era: What is the "best" therapy?

Meetu Agrawal, Ravin J. Garg, Hagop Kantarjian, Jorge Cortes

Research output: Contribution to journalReview article

Abstract

The introduction of imatinib mesylate, a Bcr-Abl1 tyrosine kinase inhibitor (TKI), has revolutionized the treatment of chronic myeloid leukemia (CML). By directly targeting the Bcr-Abl kinase, imatinib leads to durable cytogenetic remissions and in turn improved survival. However, many patients with CML develop resistance, fail to respond, or become intolerant to imatinib due to side effects. This has spurred interest in developing second-generation TKIs to overcome the mechanisms of resistance that lead to treatment failure, specifically Bcr-Abl1 kinase domain mutations. Two second-generation TKIs, nilotinib and dasatinib, are approved for the treatment of CML after imatinib failure or intolerance. Unfortunately, many patients fail subsequent treatment with these agents, as they can develop highly resistant mutations such as T315I. Various other strategies are now in use to optimize the treatment of CML, including dose optimization of imatinib, combination therapy, upfront use of second-generation TKIs, and use of maintenance therapy with interferon-α and vaccines. This review highlights progress made in the treatment of CML in the past year.

Original languageEnglish (US)
Pages (from-to)302-313
Number of pages12
JournalCurrent Oncology Reports
Volume12
Issue number5
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

Fingerprint

Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Therapeutics
Phosphotransferases
Mutation
Treatment Failure
Cytogenetics
Interferons
Vaccines
Imatinib Mesylate
Survival

Keywords

  • Chronic myeloid leukemia
  • Dasatinib
  • Imatinib
  • Nilotinib

ASJC Scopus subject areas

  • Oncology

Cite this

Chronic myeloid leukemia in the tyrosine kinase inhibitor era : What is the "best" therapy? / Agrawal, Meetu; Garg, Ravin J.; Kantarjian, Hagop; Cortes, Jorge.

In: Current Oncology Reports, Vol. 12, No. 5, 01.09.2010, p. 302-313.

Research output: Contribution to journalReview article

Agrawal, Meetu ; Garg, Ravin J. ; Kantarjian, Hagop ; Cortes, Jorge. / Chronic myeloid leukemia in the tyrosine kinase inhibitor era : What is the "best" therapy?. In: Current Oncology Reports. 2010 ; Vol. 12, No. 5. pp. 302-313.
@article{986e1e74a7734b428ffdeedd5ede957b,
title = "Chronic myeloid leukemia in the tyrosine kinase inhibitor era: What is the {"}best{"} therapy?",
abstract = "The introduction of imatinib mesylate, a Bcr-Abl1 tyrosine kinase inhibitor (TKI), has revolutionized the treatment of chronic myeloid leukemia (CML). By directly targeting the Bcr-Abl kinase, imatinib leads to durable cytogenetic remissions and in turn improved survival. However, many patients with CML develop resistance, fail to respond, or become intolerant to imatinib due to side effects. This has spurred interest in developing second-generation TKIs to overcome the mechanisms of resistance that lead to treatment failure, specifically Bcr-Abl1 kinase domain mutations. Two second-generation TKIs, nilotinib and dasatinib, are approved for the treatment of CML after imatinib failure or intolerance. Unfortunately, many patients fail subsequent treatment with these agents, as they can develop highly resistant mutations such as T315I. Various other strategies are now in use to optimize the treatment of CML, including dose optimization of imatinib, combination therapy, upfront use of second-generation TKIs, and use of maintenance therapy with interferon-α and vaccines. This review highlights progress made in the treatment of CML in the past year.",
keywords = "Chronic myeloid leukemia, Dasatinib, Imatinib, Nilotinib",
author = "Meetu Agrawal and Garg, {Ravin J.} and Hagop Kantarjian and Jorge Cortes",
year = "2010",
month = "9",
day = "1",
doi = "10.1007/s11912-010-0116-1",
language = "English (US)",
volume = "12",
pages = "302--313",
journal = "Current Oncology Reports",
issn = "1523-3790",
publisher = "Current Science, Inc.",
number = "5",

}

TY - JOUR

T1 - Chronic myeloid leukemia in the tyrosine kinase inhibitor era

T2 - What is the "best" therapy?

AU - Agrawal, Meetu

AU - Garg, Ravin J.

AU - Kantarjian, Hagop

AU - Cortes, Jorge

PY - 2010/9/1

Y1 - 2010/9/1

N2 - The introduction of imatinib mesylate, a Bcr-Abl1 tyrosine kinase inhibitor (TKI), has revolutionized the treatment of chronic myeloid leukemia (CML). By directly targeting the Bcr-Abl kinase, imatinib leads to durable cytogenetic remissions and in turn improved survival. However, many patients with CML develop resistance, fail to respond, or become intolerant to imatinib due to side effects. This has spurred interest in developing second-generation TKIs to overcome the mechanisms of resistance that lead to treatment failure, specifically Bcr-Abl1 kinase domain mutations. Two second-generation TKIs, nilotinib and dasatinib, are approved for the treatment of CML after imatinib failure or intolerance. Unfortunately, many patients fail subsequent treatment with these agents, as they can develop highly resistant mutations such as T315I. Various other strategies are now in use to optimize the treatment of CML, including dose optimization of imatinib, combination therapy, upfront use of second-generation TKIs, and use of maintenance therapy with interferon-α and vaccines. This review highlights progress made in the treatment of CML in the past year.

AB - The introduction of imatinib mesylate, a Bcr-Abl1 tyrosine kinase inhibitor (TKI), has revolutionized the treatment of chronic myeloid leukemia (CML). By directly targeting the Bcr-Abl kinase, imatinib leads to durable cytogenetic remissions and in turn improved survival. However, many patients with CML develop resistance, fail to respond, or become intolerant to imatinib due to side effects. This has spurred interest in developing second-generation TKIs to overcome the mechanisms of resistance that lead to treatment failure, specifically Bcr-Abl1 kinase domain mutations. Two second-generation TKIs, nilotinib and dasatinib, are approved for the treatment of CML after imatinib failure or intolerance. Unfortunately, many patients fail subsequent treatment with these agents, as they can develop highly resistant mutations such as T315I. Various other strategies are now in use to optimize the treatment of CML, including dose optimization of imatinib, combination therapy, upfront use of second-generation TKIs, and use of maintenance therapy with interferon-α and vaccines. This review highlights progress made in the treatment of CML in the past year.

KW - Chronic myeloid leukemia

KW - Dasatinib

KW - Imatinib

KW - Nilotinib

UR - http://www.scopus.com/inward/record.url?scp=77956265263&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956265263&partnerID=8YFLogxK

U2 - 10.1007/s11912-010-0116-1

DO - 10.1007/s11912-010-0116-1

M3 - Review article

C2 - 20640942

AN - SCOPUS:77956265263

VL - 12

SP - 302

EP - 313

JO - Current Oncology Reports

JF - Current Oncology Reports

SN - 1523-3790

IS - 5

ER -