1. Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia.
- Author
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Simonsson B, Gedde-Dahl T, Markevärn B, Remes K, Stentoft J, Almqvist A, Björeman M, Flogegård M, Koskenvesa P, Lindblom A, Malm C, Mustjoki S, Myhr-Eriksson K, Ohm L, Räsänen A, Sinisalo M, Själander A, Strömberg U, Bjerrum OW, Ehrencrona H, Gruber F, Kairisto V, Olsson K, Sandin F, Nagler A, Nielsen JL, Hjorth-Hansen H, and Porkka K
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Benzamides, Biomarkers analysis, Drug Dosage Calculations, Female, Fusion Proteins, bcr-abl analysis, Fusion Proteins, bcr-abl biosynthesis, Humans, Imatinib Mesylate, Interferon-alpha administration & dosage, Interferon-alpha adverse effects, Male, Middle Aged, Piperazines administration & dosage, Piperazines adverse effects, Polyethylene Glycols administration & dosage, Polyethylene Glycols adverse effects, Polymerase Chain Reaction, Protein-Tyrosine Kinases analysis, Protein-Tyrosine Kinases biosynthesis, Pyrimidines administration & dosage, Pyrimidines adverse effects, Recombinant Proteins administration & dosage, Recombinant Proteins adverse effects, Recombinant Proteins therapeutic use, Risk Factors, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Interferon-alpha therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Piperazines therapeutic use, Polyethylene Glycols therapeutic use, Pyrimidines therapeutic use, Remission Induction methods
- 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.
- Published
- 2011
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