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

  作者 Simonsson, B; Gedde-Dahl, T; Markevarn, B; Remes, K; Stentoft, J; Almqvist, A; Bjoreman, M; Flogegard, M; Koskenvesa, P; Lindblom, A; Malm, C; Mustjoki, S; Myhr-Eriksson, K; Ohm, L; Rasanen, A; Sinisalo, M; Sjalander, A; Stromberg, U; Bjerrum, OW; Ehrencrona, H; Gruber, F; Kairisto, V; Olsson, K; Sandin, F; Nagler, A; Nielsen, JL; Hjorth-Hansen, H; Porkka, K  
  选自 期刊  Blood;  卷期  2011年118-12;  页码  3228-3235  
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[摘要]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. (Blood. 2011;118(12):3228-3235)

 
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