ABSTRACT
INTRODUCTION: Adults with acute myeloid leukemia (AML) have a high rate of remission; however, more than 50% relapse. C-kit is expressed in approximately 60% of patients with de novo AML and represents a potential therapeutic target. MATERIALS AND METHODS: Patients with newly diagnosed AML received 12 months of imatinib mesylate as maintenance therapy after the completion of post-remission therapy. The primary objective was to determine whether this approach improved progression-free survival (defined as no relapse and no death) compared with historical controls. RESULTS: The median progression-free survival of patients < 60 years of age was 52.1 months (historical control, 13 months) and for patients ≥ 60 years of age was 10.7 months (historical control, 8 months). The median level of AF1q expression was high (9.59), and 84% of patients had moderate or high levels of drug-resistance factors. CONCLUSIONS: Imatinib maintenance therapy may improve the outcome of newly diagnosed patients with AML who are < 60 years of age.
Subject(s)
Imatinib Mesylate/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Neoplasm Recurrence, Local/drug therapy , Protein Kinase Inhibitors/administration & dosage , Proto-Oncogene Proteins c-kit/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Female , Humans , Imatinib Mesylate/adverse effects , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Maintenance Chemotherapy/methods , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Progression-Free Survival , Protein Kinase Inhibitors/adverse effects , Proto-Oncogene Proteins c-kit/metabolism , Young AdultABSTRACT
The c-kit receptor is expressed in 95% of relapsed acute myeloid leukemias (AMLs) and mediates leukemic proliferation. We conducted a Phase 1 study of the c-kit inhibitor, imatinib mesylate (IM), in combination with cytarabine and daunorubicin (7+3) in c-kit+ relapsed AML. IM was dose escalated using a 3 by 3 design. Phosphorylated STAT5 was absent to minimally present in residual blasts on day 14 bone marrows. The maximum tolerated dose of IM was 300 mg. The dose-limiting toxicity was Grade 3-4 hepatic toxicity. The CR/CRp rate was 57%. Cytotoxic therapy that includes IM for relapsed AML is well-tolerated and effective.
