Interferon alpha-2c therapy of patients with chronic myelogenous leukemia: long-term results of a multicenter phase-II study

Research paper by J. Thaler, G. Gastl, T. Fluckinger, D. Niederwieser, H. Huber, H. Seewann, H. Sill, A. Lang, M. Falk, C. Duba, G. Utermann, T. Kühr, W. Aulitzky, C. Huber, Austrian Biological Response Modifier (BRM) Study Group*

Indexed on: 01 Jun '96Published on: 01 Jun '96Published in: Annals of Hematology


 In a prospective multicenter phase-II trial 80 patients with Philadelphia (Ph)-positive chronic myelogenous leukemia (CML) were treated with recombinant interferon (IFN)α-2c, administered subcutaneously at an absolute dose of 3.5 megaunits (MU)/day. Complete hematological remission was achieved in 29 (39%) and partial hematological remission in 26 (35%) of the 74 patients evaluable for response. Major cytogenetic responses were observed in ten (13%) and minor cytogenetic responses in 11 patients (15%). Median duration of cytogenetic response was 33 months (range, 2–90); relapses were seen in all of the 11 patients with minor and in three of the ten patients with major cytogenetic responses. Median survival estimates for pretreated (n=19) and untreated (n=58) patients were 51 months (95% confidence interval [CI], 30–72) and 77 months (95% CI, 43–111), and the survival probabilities at 5 years were 45% and 54% for the two groups, respectively. Hematological response after 3 months of treatment demonstrated a clear-cut discriminative capacity with 5-year survival probabilities of 100%, 67% and 24% for patients achieving CHR (n=6), PHR (n=34), and less than PHR (n=35), respectively. Landmark analysis at 12, 18, and 24 months after start of IFN therapy and an analysis treating time to cytogenetic response as a time-dependent covariate showed that cytogenetic response was associated with longer survival. The impact of a low-dose IFN regimen on survival in CML patients is unclear and requires further clarification by randomized clinical trials. Early hematological and cytogenetic response to IFN-α treatment identifies patients with a favorable long-term prognosis.