¹Oregon Health and Science University, Division of Hematology and Medical Oncology, Portland, OR, USA

²III Medizinische Universitätsklink, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany

Correspondence to: B Druker, Orgeon Health and Science University, Division of Hematology and Medical Oncology; 3181 Sam Jackson Park Rd, mail code L592, Portland, Oregon 97201, USA; Fax: 1 503 494 3688

Clinical phase I/II studies with the Abl kinase inhibitor imatinib mesylate (Gleevec/Glivec, formerly STI571) for the treatment for chronic myelogenous leukemia (CML) demonstrated the safety and the remarkable efficacy of this molecularly targeted agent. However, a significant proportion of patients treated in the chronic phase of the disease after having failed interferon alpha (IFN) remain predominantly Philadelphia chromosome positive (Ph⁺), suggesting a risk of later relapses. Furthermore, results in blast crisis patients revealed a high frequency of relapses or resistance to imatinib. To circumvent resistance, improve response rates, or prolong survival, pre-clinical evaluations of combinations of imatinib with other agents have been pursued. Some of these have already been translated into clinical studies. Here, we first summarize evidence from pre-clinical studies on new combination regimens with imatinib in the treatment of CML. Second, we analyze preliminary clinical data of ongoing combination studies. Finally, we provide a summary of approaches that use novel antileukemic agents with molecularly characterized modes of action.

Leukemia (2002) 16, 1213-1219. doi:10.1038/sj.leu.2402555

imatinib mesylate; ST1571; combination therapy; CML