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

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 μg/kg/wk and GM‐CSF 125 mg/m2 3× 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. Cancer 2011. © 2010 American Cancer Society. Therapeutic strategies to eradicate minimal residual disease are warranted in chronic myelogenous leukemia (CML). The authors present the first report testing, in a randomized manner, the long‐term activity and tolerability of adding pegylated interferon alpha‐2b to high‐dose imatinib therapy in patients with CML in chronic phase. Although no significant differences were observed in the rates of molecular response between the treatment arms, this trial provides the foundation for future clinical trials intended to eradicate minimal residual disease in CML.