Immune modulation of minimal residual disease in early chronic phase chronic myelogenous leukemia

Jorge Cortes, Alfonso Quintás-Cardama, Dan Jones, Farhad Ravandi, Guillermo Garcia-Manero, Srdan Verstovsek, Charles Koller, Jody Hiteshew, Jenny Shan, Susan O'Brien, Hagop Kantarjian

Research output: Contribution to journalArticle

Abstract

Background: Most patients with chronic myelogenous leukemia (CML) harbor residual disease, as evidenced by molecular techniques even after treatment with high-dose imatinib (ie, 800 mg/d). Interferon alpha (IFN α) is efficacious in CML likely due to its immunomodulatory properties, and is synergistic in vitro with imatinib and granulocyte macrophage-colony stimulating factor (GM-CSF). Methods: A study was undertaken to determine whether adding pegylated (PEG) IFN α-2b and GM-CSF to high-dose imatinib may improve the complete molecular response rate in patients with CML in chronic phase. Ninety-four patients were treated with imatinib 800 mg/d for the first 6 months, then randomly assigned to continue high-dose imatinib alone (n = 49) or in combination with PEG IFN α-2b 0.5 Iμg/kg/wk and GM-CSF 125 mg/m 2 3Ã - weekly (n = 45). Results: The median follow-up for all patients was 54 months (range, 7-70 months). There were no differences in the rates of complete cytogenetic response (87% vs 90%; P = 1.0), or of major (77% vs 77%; P = 1.0) or complete (11% vs 13%; P = 1.0) molecular response (on the international scale) at 12 months between the 2 arms, or at any time during the study. Adverse events led to PEG IFN α-2b discontinuation in all patients. Conclusions: The addition of PEG IFN α-2b and GM-CSF to high-dose imatinib therapy does not improve significantly the cytogenetic or molecular response rates compared with high-dose imatinib alone. The high dropout rate in the PEG IFN α-2b arm may have compromised its potential immunomodulatory benefit.

Original languageEnglish (US)
Pages (from-to)572-580
Number of pages9
JournalCancer
Volume117
Issue number3
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Residual Neoplasm
Granulocyte-Macrophage Colony-Stimulating Factor
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
Imatinib Mesylate
Interferon-alpha
peginterferon alfa-2b
Therapeutics

Keywords

  • chronic myeloid leukemia
  • granulocyte-macrophage colony-stimulating factor
  • imatinib
  • immune modulation
  • interferon alpha-2b

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cortes, J., Quintás-Cardama, A., Jones, D., Ravandi, F., Garcia-Manero, G., Verstovsek, S., ... Kantarjian, H. (2011). Immune modulation of minimal residual disease in early chronic phase chronic myelogenous leukemia. Cancer, 117(3), 572-580. https://doi.org/10.1002/cncr.25438

Immune modulation of minimal residual disease in early chronic phase chronic myelogenous leukemia. / Cortes, Jorge; Quintás-Cardama, Alfonso; Jones, Dan; Ravandi, Farhad; Garcia-Manero, Guillermo; Verstovsek, Srdan; Koller, Charles; Hiteshew, Jody; Shan, Jenny; O'Brien, Susan; Kantarjian, Hagop.

In: Cancer, Vol. 117, No. 3, 01.02.2011, p. 572-580.

Research output: Contribution to journalArticle

Cortes, J, Quintás-Cardama, A, Jones, D, Ravandi, F, Garcia-Manero, G, Verstovsek, S, Koller, C, Hiteshew, J, Shan, J, O'Brien, S & Kantarjian, H 2011, 'Immune modulation of minimal residual disease in early chronic phase chronic myelogenous leukemia', Cancer, vol. 117, no. 3, pp. 572-580. https://doi.org/10.1002/cncr.25438
Cortes J, Quintás-Cardama A, Jones D, Ravandi F, Garcia-Manero G, Verstovsek S et al. Immune modulation of minimal residual disease in early chronic phase chronic myelogenous leukemia. Cancer. 2011 Feb 1;117(3):572-580. https://doi.org/10.1002/cncr.25438
Cortes, Jorge ; Quintás-Cardama, Alfonso ; Jones, Dan ; Ravandi, Farhad ; Garcia-Manero, Guillermo ; Verstovsek, Srdan ; Koller, Charles ; Hiteshew, Jody ; Shan, Jenny ; O'Brien, Susan ; Kantarjian, Hagop. / Immune modulation of minimal residual disease in early chronic phase chronic myelogenous leukemia. In: Cancer. 2011 ; Vol. 117, No. 3. pp. 572-580.
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abstract = "Background: Most patients with chronic myelogenous leukemia (CML) harbor residual disease, as evidenced by molecular techniques even after treatment with high-dose imatinib (ie, 800 mg/d). Interferon alpha (IFN α) is efficacious in CML likely due to its immunomodulatory properties, and is synergistic in vitro with imatinib and granulocyte macrophage-colony stimulating factor (GM-CSF). Methods: A study was undertaken to determine whether adding pegylated (PEG) IFN α-2b and GM-CSF to high-dose imatinib may improve the complete molecular response rate in patients with CML in chronic phase. Ninety-four patients were treated with imatinib 800 mg/d for the first 6 months, then randomly assigned to continue high-dose imatinib alone (n = 49) or in combination with PEG IFN α-2b 0.5 Iμg/kg/wk and GM-CSF 125 mg/m 2 3{\~A} - weekly (n = 45). Results: The median follow-up for all patients was 54 months (range, 7-70 months). There were no differences in the rates of complete cytogenetic response (87{\%} vs 90{\%}; P = 1.0), or of major (77{\%} vs 77{\%}; P = 1.0) or complete (11{\%} vs 13{\%}; P = 1.0) molecular response (on the international scale) at 12 months between the 2 arms, or at any time during the study. Adverse events led to PEG IFN α-2b discontinuation in all patients. Conclusions: The addition of PEG IFN α-2b and GM-CSF to high-dose imatinib therapy does not improve significantly the cytogenetic or molecular response rates compared with high-dose imatinib alone. The high dropout rate in the PEG IFN α-2b arm may have compromised its potential immunomodulatory benefit.",
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AU - Cortes, Jorge

AU - Quintás-Cardama, Alfonso

AU - Jones, Dan

AU - Ravandi, Farhad

AU - Garcia-Manero, Guillermo

AU - Verstovsek, Srdan

AU - Koller, Charles

AU - Hiteshew, Jody

AU - Shan, Jenny

AU - O'Brien, Susan

AU - Kantarjian, Hagop

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N2 - Background: Most patients with chronic myelogenous leukemia (CML) harbor residual disease, as evidenced by molecular techniques even after treatment with high-dose imatinib (ie, 800 mg/d). Interferon alpha (IFN α) is efficacious in CML likely due to its immunomodulatory properties, and is synergistic in vitro with imatinib and granulocyte macrophage-colony stimulating factor (GM-CSF). Methods: A study was undertaken to determine whether adding pegylated (PEG) IFN α-2b and GM-CSF to high-dose imatinib may improve the complete molecular response rate in patients with CML in chronic phase. Ninety-four patients were treated with imatinib 800 mg/d for the first 6 months, then randomly assigned to continue high-dose imatinib alone (n = 49) or in combination with PEG IFN α-2b 0.5 Iμg/kg/wk and GM-CSF 125 mg/m 2 3Ã - weekly (n = 45). Results: The median follow-up for all patients was 54 months (range, 7-70 months). There were no differences in the rates of complete cytogenetic response (87% vs 90%; P = 1.0), or of major (77% vs 77%; P = 1.0) or complete (11% vs 13%; P = 1.0) molecular response (on the international scale) at 12 months between the 2 arms, or at any time during the study. Adverse events led to PEG IFN α-2b discontinuation in all patients. Conclusions: The addition of PEG IFN α-2b and GM-CSF to high-dose imatinib therapy does not improve significantly the cytogenetic or molecular response rates compared with high-dose imatinib alone. The high dropout rate in the PEG IFN α-2b arm may have compromised its potential immunomodulatory benefit.

AB - Background: Most patients with chronic myelogenous leukemia (CML) harbor residual disease, as evidenced by molecular techniques even after treatment with high-dose imatinib (ie, 800 mg/d). Interferon alpha (IFN α) is efficacious in CML likely due to its immunomodulatory properties, and is synergistic in vitro with imatinib and granulocyte macrophage-colony stimulating factor (GM-CSF). Methods: A study was undertaken to determine whether adding pegylated (PEG) IFN α-2b and GM-CSF to high-dose imatinib may improve the complete molecular response rate in patients with CML in chronic phase. Ninety-four patients were treated with imatinib 800 mg/d for the first 6 months, then randomly assigned to continue high-dose imatinib alone (n = 49) or in combination with PEG IFN α-2b 0.5 Iμg/kg/wk and GM-CSF 125 mg/m 2 3Ã - weekly (n = 45). Results: The median follow-up for all patients was 54 months (range, 7-70 months). There were no differences in the rates of complete cytogenetic response (87% vs 90%; P = 1.0), or of major (77% vs 77%; P = 1.0) or complete (11% vs 13%; P = 1.0) molecular response (on the international scale) at 12 months between the 2 arms, or at any time during the study. Adverse events led to PEG IFN α-2b discontinuation in all patients. Conclusions: The addition of PEG IFN α-2b and GM-CSF to high-dose imatinib therapy does not improve significantly the cytogenetic or molecular response rates compared with high-dose imatinib alone. The high dropout rate in the PEG IFN α-2b arm may have compromised its potential immunomodulatory benefit.

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