Combination of pegylated IFN-alpha 2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia

• Published in: Blood Vol. 118; no. 12; p. 3228
• Main Authors: Simonsson, Bengt, Gedde-Dahl, Tobias, Markevarn, Berit, Remes, Kari, Stentoft, Jesper, Almqvist, Anders, Bjoreman, Mats, Flogegard, Max, Koskenvesa, Perttu, Lindblom, Anders, Malm, Claes, Mustjoki, Satu, Myhr-Eriksson, Kristina, Ohm, Lotta, Rasanen, Anu, Sinisalo, Marjatta, Sjalander, Anders, Stromberg, Ulla, Weiss Bjerrum, Ole, Ehrencrona, Hans, Gruber, Franz, Kairisto, Veli, Olsson, Karin, Sandin, Fredrik, Nagler, Arnon, Lanng Nielsen, Johan, Hjorth-Hansen, Henrik, Porkka, Kimmo
• Format: Journal Article
• Language: English
• Published: 2011
• Subjects: Clinical Medicine; Hematologi; Hematology; Klinisk medicin; Medical and Health Sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-02-336685

Biologic and clinical observations suggest that combining imatinib with IFN-alpha 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-alpha 2b (Peg-IFN-alpha 2b) 50 mu g 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-alpha 2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-alpha 2b arm (82%) compared with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-alpha 2b treatment (< 12-week MMR rate 67%, > 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-alpha 2b to imatinib markedly increased the MMR rate at 12 months of therapy. Lower doses of Peg-IFN-alpha 2b may enhance tolerability while retaining efficacy and could be considered in future protocols with curative intent.