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

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 alpha) 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 alpha-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 alpha-2b 0.5 mu g/kg/wk and GM-CSF 125 mg/m(2) 3 x 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 alpha-2b discontinuation in all patients. CONCLUSIONS: The addition of PEG IFN alpha-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 alpha-2b arm may have compromised its potential immunomodulatory benefit. Cancer 2011;117:572-80. (C) 2010 American Cancer Society.