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The Interferon-Alpha Revival in CML

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Chronic Myeloid Leukemia

Part of the book series: Hematologic Malignancies ((HEMATOLOGIC))

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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 it could induce 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, achieve remarkable responses in CML patients and have become the mainstay of CML therapy. Although TKIs target the pathogenic BCR-ABL1 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. Furthermore, emerging data from combination trials with second-generation TKIs suggest long-term use of IFNα may deepen molecular responses in CML patients. 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 unclear. Further studies are needed to clarify the best niche for IFNα use in CML.

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Hematology Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA

    Moshe Talpaz & Jessica Mercer

  2. ELN Foundation, Weinheim, Germany

    Rüdiger Hehlmann

  3. Medizinische Fakultät Mannheim, Universität Heidelberg, III.Medizinische Klink, Mannheim, Germany

    Rüdiger Hehlmann

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  1. Moshe Talpaz
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  2. Jessica Mercer
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  3. Rüdiger Hehlmann
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Correspondence to Moshe Talpaz .

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  1. ELN Foundation, Weinheim, Germany

    Rüdiger Hehlmann

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MT has chaired a satellite symposium for Merck and has received drugs from Merck for clinical studies. The remaining authors declare no conflict of interest.

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Talpaz, M., Mercer, J., Hehlmann, R. (2021). The Interferon-Alpha Revival in CML. In: Hehlmann, R. (eds) Chronic Myeloid Leukemia. Hematologic Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-030-71913-5_13

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