TY - JOUR
T1 - Re-emergence of interferon-α in the treatment of chronic myeloid leukemia
AU - Talpaz, M.
AU - Hehlmann, R.
AU - Quintás-Cardama, A.
AU - Mercer, J.
AU - Cortes, J.
N1 - Funding Information:
JC is a consultant for and has received research funding from BMS, Novartis, Ariad and Chemgenex. 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.
PY - 2013/4
Y1 - 2013/4
N2 - Treatment for chronic myeloid leukemia (CML) has evolved from chemotherapy (busulfan, hydroxyurea) to interferon-α (IFNα), and finally to tyrosine kinase inhibitors such as imatinib. Although imatinib has profoundly improved outcomes for patients with CML, it has limitations. Most significantly, imatinib cannot eradicate CML primitive progenitors, which likely accounts for the high relapse rate when imatinib is discontinued. IFNα, unlike imatinib, preferentially targets CML stem cells. Early studies with IFNα in CML demonstrated its ability to induce cytogenetic remission. Moreover, a small percentage of patients treated with IFNα were able to sustain durable remissions after discontinuing therapy and were probably cured. The mechanisms by which IFNα exerts its antitumor activity in CML are not well understood; however, activation of leukemia-specific immunity may have a role. Some clinical studies have demonstrated that the combination of imatinib and IFNα is superior to either therapy alone, perhaps because of their different mechanisms of action. Nonetheless, the side effects of IFNα often impede its administration, especially in combination therapy. Here, we review the role of IFNα in CML treatment and the recent developments that have renewed interest in this once standard therapy for patients with CML.
AB - Treatment for chronic myeloid leukemia (CML) has evolved from chemotherapy (busulfan, hydroxyurea) to interferon-α (IFNα), and finally to tyrosine kinase inhibitors such as imatinib. Although imatinib has profoundly improved outcomes for patients with CML, it has limitations. Most significantly, imatinib cannot eradicate CML primitive progenitors, which likely accounts for the high relapse rate when imatinib is discontinued. IFNα, unlike imatinib, preferentially targets CML stem cells. Early studies with IFNα in CML demonstrated its ability to induce cytogenetic remission. Moreover, a small percentage of patients treated with IFNα were able to sustain durable remissions after discontinuing therapy and were probably cured. The mechanisms by which IFNα exerts its antitumor activity in CML are not well understood; however, activation of leukemia-specific immunity may have a role. Some clinical studies have demonstrated that the combination of imatinib and IFNα is superior to either therapy alone, perhaps because of their different mechanisms of action. Nonetheless, the side effects of IFNα often impede its administration, especially in combination therapy. Here, we review the role of IFNα in CML treatment and the recent developments that have renewed interest in this once standard therapy for patients with CML.
KW - chronic myeloid leukemia
KW - imatinib
KW - interferon-a
KW - tyrosine kinase inhibitor
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U2 - 10.1038/leu.2012.313
DO - 10.1038/leu.2012.313
M3 - Review article
C2 - 23238589
AN - SCOPUS:84876100195
SN - 0887-6924
VL - 27
SP - 803
EP - 812
JO - Leukemia
JF - Leukemia
IS - 4
ER -