Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia

• Published in: Blood Vol. 118; no. 12; pp. 3228 - 3235
• Main Authors: Simonsson, Bengt, Gedde-Dahl, Tobias, Markevärn, Berit, Remes, Kari, Stentoft, Jesper, Almqvist, Anders, Björeman, Mats, Flogegård, Max, Koskenvesa, Perttu, Lindblom, Anders, Malm, Claes, Mustjoki, Satu, Myhr-Eriksson, Kristina, Ohm, Lotta, Räsänen, Anu, Sinisalo, Marjatta, Själander, Anders, Strömberg, Ulla, Bjerrum, Ole Weiss, Ehrencrona, Hans, Gruber, Franz, Kairisto, Veli, Olsson, Karin, Sandin, Fredrik, Nagler, Arnon, Nielsen, Johan Lanng, Hjorth-Hansen, Henrik, Porkka, Kimmo
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 22.09.2011; Americain Society of Hematology
• Subjects: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzamides; Biological and medical sciences; Biomarkers - analysis; Drug Dosage Calculations; Female; Fusion Proteins, bcr-abl - analysis; Fusion Proteins, bcr-abl - biosynthesis; Hematologic and hematopoietic diseases; Humans; Imatinib Mesylate; Interferon-alpha - administration & dosage; Interferon-alpha - adverse effects; 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; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Piperazines - administration & dosage; Piperazines - adverse effects; Piperazines - therapeutic use; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - adverse effects; Polyethylene Glycols - therapeutic use; Polymerase Chain Reaction; Protein-Tyrosine Kinases - analysis; Protein-Tyrosine Kinases - biosynthesis; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Remission Induction - methods; Risk Factors; Treatment Outcome; Antineoplastic agent; Human; Imatinib; Hematology; Enzyme; Tyrosine kinase inhibitor; Transferases; Cytokine; Enzyme inhibitor; Chronic myelogenous leukemia; Response rate; Malignant hemopathy; Low risk; Myeloproliferative syndrome; Interferon alpha 2b; Pegylated form; Protein-tyrosine kinase; Cancer
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-02-336685

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.