The interferon-alpha revival in CML

Abstract

Interferon-alpha (IFNα) was once the standard of frontline treatment for chronic myeloid leukemia (CML). Its pleiotropic mechanism of action in CML includes immune activation and specific targeting of CML stem cells. Early studies of IFNα in CML demonstrated that patients in chronic phase could attain extremely stable remissions, which correlated with long-term survival. Some patients even sustained their remission after discontinuing therapy, but the mechanism underlying this phenomenon is not well understood. Today, BCR-ABL tyrosine kinase inhibitors (TKIs), such as imatinib, induce remarkable responses in CML patients and have become the mainstay of CML therapy. Although TKIs target the pathogenic BCR-ABL protein in CML, they cannot fully eradicate CML stem cells. Some of the clinical trials testing IFNα plus imatinib combination therapy suggest that addition of IFNα increases the speed and rate of responses with imatinib therapy. However, the undesirable side effects of IFNα can make this therapy difficult to deliver, and the optimal therapeutic window for using IFNα in combination therapy is unknown. Further studies are needed to clarify the best niche for IFNα use in CML.