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Immune modulation of minimal residual disease in early chronic phase chronic myelogenous leukemia
A randomized trial of frontline high-dose imatinib mesylate with or without pegylated interferon alpha-2b and granulocyte-macrophage colony-stimulating factor
Article first published online: 30 SEP 2010
Copyright © 2010 American Cancer Society
Volume 117, Issue 3, pages 572–580, 1 February 2011
How to Cite
Cortes, J., Quintás-Cardama, A., Jones, D., Ravandi, F., Garcia-Manero, G., Verstovsek, S., Koller, C., Hiteshew, J., Shan, J., O'Brien, S. and Kantarjian, H. (2011), Immune modulation of minimal residual disease in early chronic phase chronic myelogenous leukemia. Cancer, 117: 572–580. doi: 10.1002/cncr.25438
- Issue published online: 20 JAN 2011
- Article first published online: 30 SEP 2010
- Manuscript Accepted: 9 MAR 2010
- Manuscript Revised: 7 FEB 2010
- Manuscript Received: 23 NOV 2009
- chronic myeloid leukemia;
- granulocyte-macrophage colony-stimulating factor;
- immune modulation;
- interferon alpha-2b
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).
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 μg/kg/wk and GM-CSF 125 mg/m2 3× weekly (n = 45).
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.
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. Cancer 2011. © 2010 American Cancer Society.