Abstract
Biologic and clinical observations suggest that combining imatinib with IFN-α may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission either to receive a combination of pegylated IFN-α2b (Peg-IFN-α2b) 50 μg weekly and imatinib 400 mg daily (n = 56) or to receive imatinib 400 mg daily monotherapy (n = 56). The primary endpoint was the major molecular response (MMR) rate at 12 months after randomization. In both arms, 4 patients (7%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg-IFN-α2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-α2b arm (82%) compared with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-α2b treatment (< 12-week MMR rate 67%, > 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-α2b to imatinib markedly increased the MMR rate at 12 months of therapy. Lower doses of Peg-IFN-α2b may enhance tolerability while retaining efficacy and could be considered in future protocols with curative intent.
Publication types
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Clinical Trial, Phase II
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Multicenter Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Benzamides
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Biomarkers / analysis
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Drug Dosage Calculations
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Female
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Fusion Proteins, bcr-abl / analysis
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Fusion Proteins, bcr-abl / biosynthesis
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Humans
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Imatinib Mesylate
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Interferon-alpha / administration & dosage
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Interferon-alpha / adverse effects
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Interferon-alpha / therapeutic use*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / metabolism
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / pathology
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Male
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Middle Aged
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Piperazines / administration & dosage
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Piperazines / adverse effects
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Piperazines / therapeutic use*
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Polyethylene Glycols / administration & dosage
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Polyethylene Glycols / adverse effects
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Polyethylene Glycols / therapeutic use*
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Polymerase Chain Reaction
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Protein-Tyrosine Kinases / analysis
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Protein-Tyrosine Kinases / biosynthesis
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Pyrimidines / administration & dosage
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Pyrimidines / adverse effects
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Pyrimidines / therapeutic use*
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / adverse effects
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Recombinant Proteins / therapeutic use
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Remission Induction / methods*
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Risk Factors
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Treatment Outcome
Substances
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Benzamides
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Biomarkers
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Interferon-alpha
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Piperazines
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Pyrimidines
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Recombinant Proteins
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Polyethylene Glycols
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Imatinib Mesylate
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Protein-Tyrosine Kinases
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Fusion Proteins, bcr-abl
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peginterferon alfa-2a