Granulocyte-macrophage colony stimulating factor (GM-CSF) enhances the clinical responses to interferon-α (IFN) in newly diagnosed chronic myeloid leukemia (CML)

• IFN + GM-CSF may enhance the possibility of cure in CML by targeting the immune system and BCR-ABL1 progenitor cells.
• IFN combined with GM-CSF appears to be safe and effective in patients with CML.
• A proportion of patients treated with IFN and GM-CSF appear to be cured with no evidence of residual disease.
• IFN + GM-CSF should be further studied in CML in order to eradicate BCR-ABL1 progenitor cells and increase the chances of long-term cure.

The majority of chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) remain with residual disease. In contrast to TKIs, interferon (IFN) is directly toxic to CML progenitor cells, and myeloid growth factors such as GM-CSF may enhance IFN's cytotoxicity. We performed a phase 2 study of IFN + GM-CSF in 58 newly diagnosed CML patients before imatinib approval. Short-term clinical responses included: 60% major cytogenetic response, 28% complete cytogenetic response and 19% complete molecular response. Six patients remain off all therapy for CML (range: 15 months–12 years) after IFN + GM-CSF treatment. IFN + GM-CSF shows promise as an adjunctive therapy for CML.