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

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37 Scopus citations

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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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., 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, 117(3), 572-580. https://doi.org/10.1002/cncr.25438