Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia
Bengt Simonsson, Tobias Gedde-Dahl, Berit Markevärn, Kari Remes, Jesper Stentoft, Anders Almqvist, Mats Björeman, Max Flogegård, Perttu Koskenvesa, Anders Lindblom, Claes Malm, Satu Mustjoki, Kristina Myhr-Eriksson, Lotta Ohm, Anu Räsänen, Marjatta Sinisalo, Anders Själander, Ulla Strömberg, Ole Weiss Bjerrum, Hans Ehrencrona, Franz Gruber, Veli Kairisto, Karin Olsson, Fredrik Sandin, Arnon Nagler, Johan Lanng Nielsen, Henrik Hjorth-Hansen, Kimmo Porkka, Nordic CML Study Group, Bengt Simonsson, Tobias Gedde-Dahl, Berit Markevärn, Kari Remes, Jesper Stentoft, Anders Almqvist, Mats Björeman, Max Flogegård, Perttu Koskenvesa, Anders Lindblom, Claes Malm, Satu Mustjoki, Kristina Myhr-Eriksson, Lotta Ohm, Anu Räsänen, Marjatta Sinisalo, Anders Själander, Ulla Strömberg, Ole Weiss Bjerrum, Hans Ehrencrona, Franz Gruber, Veli Kairisto, Karin Olsson, Fredrik Sandin, Arnon Nagler, Johan Lanng Nielsen, Henrik Hjorth-Hansen, Kimmo Porkka, Nordic CML Study Group
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.
Source: PubMed