Chronic Myeloid Leukemia and Second-Generation Tyrosine Kinase Inhibitors: When, How, and Which One?

Elias Jabbour, Hagop Kantarjian, Jorge Cortes

Research output: Contribution to journalArticle

Abstract

Chronic myeloid leukemia (CML) is a progressive and often fatal myeloproliferative disorder. The introduction of imatinib, a tyrosine kinase inhibitor (TKI) specific for BCR-ABL, was a major breakthrough in CML therapy. Although most patients respond to first-line imatinib therapy, some experience a loss of response (resistance) or require treatment discontinuation due to toxicity (intolerance). For patients who fail with standard-dose imatinib therapy, imatinib dose escalation is a second-line option. However, high-dose imatinib is not an appropriate approach for patients experiencing drug toxicity, and there remain questions over the durability of responses achieved with this strategy. Alternative second-line options include the newer TKIs dasatinib and nilotinib. A substantial amount of long-term data for these agents is available. Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as disease stage and BCR-ABL mutational status. To optimize therapeutic benefit, clinicians should select treatment based on each patient's historical response, adverse-event tolerance level, and risk factors.

Original languageEnglish (US)
Pages (from-to)344-353
Number of pages10
JournalSeminars in Hematology
Volume47
Issue number4
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

Fingerprint

Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Therapeutics
Myeloproliferative Disorders
Drug-Related Side Effects and Adverse Reactions
Imatinib Mesylate
Pharmacology

ASJC Scopus subject areas

  • Hematology

Cite this

Chronic Myeloid Leukemia and Second-Generation Tyrosine Kinase Inhibitors : When, How, and Which One? / Jabbour, Elias; Kantarjian, Hagop; Cortes, Jorge.

In: Seminars in Hematology, Vol. 47, No. 4, 01.10.2010, p. 344-353.

Research output: Contribution to journalArticle

@article{d9ca3bab6bd24baaa88a53659769e836,
title = "Chronic Myeloid Leukemia and Second-Generation Tyrosine Kinase Inhibitors: When, How, and Which One?",
abstract = "Chronic myeloid leukemia (CML) is a progressive and often fatal myeloproliferative disorder. The introduction of imatinib, a tyrosine kinase inhibitor (TKI) specific for BCR-ABL, was a major breakthrough in CML therapy. Although most patients respond to first-line imatinib therapy, some experience a loss of response (resistance) or require treatment discontinuation due to toxicity (intolerance). For patients who fail with standard-dose imatinib therapy, imatinib dose escalation is a second-line option. However, high-dose imatinib is not an appropriate approach for patients experiencing drug toxicity, and there remain questions over the durability of responses achieved with this strategy. Alternative second-line options include the newer TKIs dasatinib and nilotinib. A substantial amount of long-term data for these agents is available. Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as disease stage and BCR-ABL mutational status. To optimize therapeutic benefit, clinicians should select treatment based on each patient's historical response, adverse-event tolerance level, and risk factors.",
author = "Elias Jabbour and Hagop Kantarjian and Jorge Cortes",
year = "2010",
month = "10",
day = "1",
doi = "10.1053/j.seminhematol.2010.06.002",
language = "English (US)",
volume = "47",
pages = "344--353",
journal = "Seminars in Hematology",
issn = "0037-1963",
publisher = "W.B. Saunders Ltd",
number = "4",

}

TY - JOUR

T1 - Chronic Myeloid Leukemia and Second-Generation Tyrosine Kinase Inhibitors

T2 - When, How, and Which One?

AU - Jabbour, Elias

AU - Kantarjian, Hagop

AU - Cortes, Jorge

PY - 2010/10/1

Y1 - 2010/10/1

N2 - Chronic myeloid leukemia (CML) is a progressive and often fatal myeloproliferative disorder. The introduction of imatinib, a tyrosine kinase inhibitor (TKI) specific for BCR-ABL, was a major breakthrough in CML therapy. Although most patients respond to first-line imatinib therapy, some experience a loss of response (resistance) or require treatment discontinuation due to toxicity (intolerance). For patients who fail with standard-dose imatinib therapy, imatinib dose escalation is a second-line option. However, high-dose imatinib is not an appropriate approach for patients experiencing drug toxicity, and there remain questions over the durability of responses achieved with this strategy. Alternative second-line options include the newer TKIs dasatinib and nilotinib. A substantial amount of long-term data for these agents is available. Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as disease stage and BCR-ABL mutational status. To optimize therapeutic benefit, clinicians should select treatment based on each patient's historical response, adverse-event tolerance level, and risk factors.

AB - Chronic myeloid leukemia (CML) is a progressive and often fatal myeloproliferative disorder. The introduction of imatinib, a tyrosine kinase inhibitor (TKI) specific for BCR-ABL, was a major breakthrough in CML therapy. Although most patients respond to first-line imatinib therapy, some experience a loss of response (resistance) or require treatment discontinuation due to toxicity (intolerance). For patients who fail with standard-dose imatinib therapy, imatinib dose escalation is a second-line option. However, high-dose imatinib is not an appropriate approach for patients experiencing drug toxicity, and there remain questions over the durability of responses achieved with this strategy. Alternative second-line options include the newer TKIs dasatinib and nilotinib. A substantial amount of long-term data for these agents is available. Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as disease stage and BCR-ABL mutational status. To optimize therapeutic benefit, clinicians should select treatment based on each patient's historical response, adverse-event tolerance level, and risk factors.

UR - http://www.scopus.com/inward/record.url?scp=77957096041&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957096041&partnerID=8YFLogxK

U2 - 10.1053/j.seminhematol.2010.06.002

DO - 10.1053/j.seminhematol.2010.06.002

M3 - Article

C2 - 20875551

AN - SCOPUS:77957096041

VL - 47

SP - 344

EP - 353

JO - Seminars in Hematology

JF - Seminars in Hematology

SN - 0037-1963

IS - 4

ER -