Survival Advantage with Imatinib Mesylate Therapy in Chronic-Phase Chronic Myelogenous Leukemia (CML-CP) after IFN-α Failure and in Late CML-CP, Comparison with Historical Controls

Purpose: The purpose of this research was to compare the survival of patients with Philadelphia chromosome (Ph) -positive chronic myelogenous leukemia (CML) post-IFN-α failure treated with imatinib to historical experiences with standards of care or other therapies. Experimental Design: The outcome of 261 patients with Ph-positive chronic phase CML post-IFN failure treated with imatinib was compared with 204 historical control patients treated for a similar disease status with existing therapies. A subset of 147 patients in late chronic phase CML and 100% Ph-positive status treated with imatinib was compared with 95 patients in a similar disease status treated with IFN. Multivariate analyses were conducted to assess the independent prognostic effect of therapy (imatinib versus other) on survival. Results: In the first analysis involving 261 patients on imatinib plus 204 historical patients, the complete cytogenetic response rates were 62% and 19%, respectively (P < 0.001). A multivariate analysis identified pretreatment peripheral blasts and thrombocytosis to be independent poor prognostic factors for survival. Imatinib therapy (versus others) was a significant independent favorable prognostic factor for survival (hazard ratio, 0.17; P < 0.0001). In the second analysis involving the subset of 147 patients receiving imatinib plus 95 historical patients treated with IFN regimens, the complete cytogenetic response rates were 41% and 7%, respectively (P < 0.001). A multivariate analysis selected pretreatment anemia and peripheral blasts to be significant independent poor prognostic factors for survival. Imatinib therapy (versus IFN) was an independent favorable prognostic factor for survival (hazard ratio, 0.20; P < 0.0001). Three-month and 6-month landmark analyses showed that patients in all cytogenetic response categories (major, minor, and none) after imatinib therapy had survival outcomes better than the historical control population. Within each cytogenetic response category, survival was also better with imatinib than with other therapies. Conclusions: This analysis provides evidence for a survival advantage with imatinib versus other therapies in chronic-phase CML post-IFN failure, and for a survival advantage with imatinib versus IFN in late chronic-phase CML.