Analysis of the impact of imatinib mesylate therapy on the prognosis of patients with Philadelphia chromosome-positive chronic myelogenous leukemia treated with interferon-alpha regimens for early chronic phase

Abstract

Background: The effect on prognosis of adding imatinib mesylate to the treatment of patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) has not been explored fully. The objective of the current study was to evaluate the benefit of adding imatinib to the treatment sequence of patients with early chronic phase Ph-positive CML who received interferon alpha (IFN)-based regimens as frontline therapy.

Methods: A total of 201 patients with early chronic phase Ph-positive CML who were treated on our 3 recent frontline IFN-based programs and were impacted early by the availability of sequential therapy with imatinib were analyzed. Their outcome was compared with that of a historical control group of 293 patients treated from 1982 until 1990 who were treated with IFN programs for early chronic phase CML and who did not have the opportunity of early access to imatinib (because it was not available during that period). Multivariate analysis was used to evaluate the independent effect of imatinib therapy on survival.

Results: Of 201 patients who were treated, 159 patients (79%) had their regimen changed sequentially to imatinib after a median duration of 14 months of IFN therapy. Of 139 patients who continued evaluation at our institution, 101 patients (73%; 64% of the total group) achieved a complete cytogenetic response, and 20 of 80 patients analyzed (25%; 10% of the total group) had no disease according to molecular studies (quantitative polymerase chain reaction studies). The estimated 5-year survival rate for the total study group of 201 patients was 86%. Survival of this group was significantly superior to the historic control group of IFN-treated patients who did not have the benefit of imatinib (P = 0.03). The trend also was observed within defined CML risk groups. Imatinib therapy was confirmed as an independent, significant, favorable prognostic factor for survival by multivariate analysis, after accounting for the independent prognostic effect of pretreatment prognostic factors (P = 0.005).

Conclusions: The current analysis is the first to indicate the independent, favorable effect of imatinib on the survival of patients with Ph-positive CML.