Current issues in chronic myeloid leukemia: Monitoring, resistance, and functional cure

Jorge Cortes, John M. Goldman, Timothy Hughes

Research output: Contribution to journalReview article

Abstract

Despite the success with tyrosine kinase inhibitors (TKIs) in most patients with chronic myelogenous leukemia (CML), some patients still experience resistance or intolerance and need alternative therapies. Monitoring response to TKI therapy is a critical component of managing CML, and molecular response seems to be the most important milestone for predicting long-term outcomes. How best to assess response, including how to define treatment failure, and how monitoring should be conducted remain controversial. Strategies for overcoming imatinib resistance include increasing the imatinib dose or switching to a second-generation TKI. Another approach is to use higher doses of imatinib or second-generation TKIs up front to increase the rate of earlier responses, with the hope that this will translate into a reduced risk of resistance. Several investigational therapies are also being evaluated as a means of overcoming TKI resistance, including ponatinib (AP24534), omacetaxine, and bosutinib (SKI-606). Allogeneic hematopoietic stem cell transplantation has also shown efficacy in patients with imatinib-resistant disease. Alternatives to long-term TKI therapy that are currently being explored include discontinuation of treatment and eradication of minimal residual disease with investigational treatment regimens, such as those involving interferon, hydroxychloroquine, BCL6 inhibitors, and the smoothened antagonists LDF225 and BMS-833923.

Original languageEnglish (US)
Pages (from-to)S1-S13
JournalJNCCN Journal of the National Comprehensive Cancer Network
Volume10
Issue numberSUPPL.3
StatePublished - Dec 21 2012
Externally publishedYes

Fingerprint

Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Investigational Therapies
Hydroxychloroquine
Hematopoietic Stem Cell Transplantation
Residual Neoplasm
Complementary Therapies
Treatment Failure
Interferons
Therapeutics
Imatinib Mesylate

ASJC Scopus subject areas

  • Oncology

Cite this

Current issues in chronic myeloid leukemia : Monitoring, resistance, and functional cure. / Cortes, Jorge; Goldman, John M.; Hughes, Timothy.

In: JNCCN Journal of the National Comprehensive Cancer Network, Vol. 10, No. SUPPL.3, 21.12.2012, p. S1-S13.

Research output: Contribution to journalReview article

@article{de44892861174b8a82dbc4569921e6e7,
title = "Current issues in chronic myeloid leukemia: Monitoring, resistance, and functional cure",
abstract = "Despite the success with tyrosine kinase inhibitors (TKIs) in most patients with chronic myelogenous leukemia (CML), some patients still experience resistance or intolerance and need alternative therapies. Monitoring response to TKI therapy is a critical component of managing CML, and molecular response seems to be the most important milestone for predicting long-term outcomes. How best to assess response, including how to define treatment failure, and how monitoring should be conducted remain controversial. Strategies for overcoming imatinib resistance include increasing the imatinib dose or switching to a second-generation TKI. Another approach is to use higher doses of imatinib or second-generation TKIs up front to increase the rate of earlier responses, with the hope that this will translate into a reduced risk of resistance. Several investigational therapies are also being evaluated as a means of overcoming TKI resistance, including ponatinib (AP24534), omacetaxine, and bosutinib (SKI-606). Allogeneic hematopoietic stem cell transplantation has also shown efficacy in patients with imatinib-resistant disease. Alternatives to long-term TKI therapy that are currently being explored include discontinuation of treatment and eradication of minimal residual disease with investigational treatment regimens, such as those involving interferon, hydroxychloroquine, BCL6 inhibitors, and the smoothened antagonists LDF225 and BMS-833923.",
author = "Jorge Cortes and Goldman, {John M.} and Timothy Hughes",
year = "2012",
month = "12",
day = "21",
language = "English (US)",
volume = "10",
pages = "S1--S13",
journal = "Journal of the National Comprehensive Cancer Network : JNCCN",
issn = "1540-1405",
publisher = "Cold Spring Publishing LLC",
number = "SUPPL.3",

}

TY - JOUR

T1 - Current issues in chronic myeloid leukemia

T2 - Monitoring, resistance, and functional cure

AU - Cortes, Jorge

AU - Goldman, John M.

AU - Hughes, Timothy

PY - 2012/12/21

Y1 - 2012/12/21

N2 - Despite the success with tyrosine kinase inhibitors (TKIs) in most patients with chronic myelogenous leukemia (CML), some patients still experience resistance or intolerance and need alternative therapies. Monitoring response to TKI therapy is a critical component of managing CML, and molecular response seems to be the most important milestone for predicting long-term outcomes. How best to assess response, including how to define treatment failure, and how monitoring should be conducted remain controversial. Strategies for overcoming imatinib resistance include increasing the imatinib dose or switching to a second-generation TKI. Another approach is to use higher doses of imatinib or second-generation TKIs up front to increase the rate of earlier responses, with the hope that this will translate into a reduced risk of resistance. Several investigational therapies are also being evaluated as a means of overcoming TKI resistance, including ponatinib (AP24534), omacetaxine, and bosutinib (SKI-606). Allogeneic hematopoietic stem cell transplantation has also shown efficacy in patients with imatinib-resistant disease. Alternatives to long-term TKI therapy that are currently being explored include discontinuation of treatment and eradication of minimal residual disease with investigational treatment regimens, such as those involving interferon, hydroxychloroquine, BCL6 inhibitors, and the smoothened antagonists LDF225 and BMS-833923.

AB - Despite the success with tyrosine kinase inhibitors (TKIs) in most patients with chronic myelogenous leukemia (CML), some patients still experience resistance or intolerance and need alternative therapies. Monitoring response to TKI therapy is a critical component of managing CML, and molecular response seems to be the most important milestone for predicting long-term outcomes. How best to assess response, including how to define treatment failure, and how monitoring should be conducted remain controversial. Strategies for overcoming imatinib resistance include increasing the imatinib dose or switching to a second-generation TKI. Another approach is to use higher doses of imatinib or second-generation TKIs up front to increase the rate of earlier responses, with the hope that this will translate into a reduced risk of resistance. Several investigational therapies are also being evaluated as a means of overcoming TKI resistance, including ponatinib (AP24534), omacetaxine, and bosutinib (SKI-606). Allogeneic hematopoietic stem cell transplantation has also shown efficacy in patients with imatinib-resistant disease. Alternatives to long-term TKI therapy that are currently being explored include discontinuation of treatment and eradication of minimal residual disease with investigational treatment regimens, such as those involving interferon, hydroxychloroquine, BCL6 inhibitors, and the smoothened antagonists LDF225 and BMS-833923.

UR - http://www.scopus.com/inward/record.url?scp=84871191881&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871191881&partnerID=8YFLogxK

M3 - Review article

C2 - 23055247

AN - SCOPUS:84871191881

VL - 10

SP - S1-S13

JO - Journal of the National Comprehensive Cancer Network : JNCCN

JF - Journal of the National Comprehensive Cancer Network : JNCCN

SN - 1540-1405

IS - SUPPL.3

ER -