Pilot study of Mylotarg, idarubicin and cytarabine combination regimen in patients with primary resistant or relapsed acute myeloid leukemia

Abstract

Purpose. Mylotarg has moderate activity as a single agent in patients with CD33-positive refractory or relapsed acute myelogenous leukemia (AML). A combination of an anthracycline and cytarabine (ara-C) is the core of most AML induction regimens. We conducted a pilot study of Mylotarg combined with idarubicin and ara-C in patients with refractory or relapsed AML.

Methods. Mylotarg was administered at 6 mg/m² intravenously on days 1 and 15, idarubicin 12 mg/m² daily on days 2 through 4, and ara-C at 1.5 g/m² daily on days 2 through 5 (MIA)

Results. Of 14 patients were treated, 4 (29%) had primary resistant AML, and 10 (71%) relapsed AML. The median age of the patients was 61 years (range 34–74 years). MIA induced complete remission (CR) in three patients (21%) and CR with incomplete platelet recovery (CRp) in three patients (21%). The median survival was 8 weeks (range 2–64 weeks), and the median failure-free survival of CR patients was 27 weeks (range 11–64 weeks). All patients developed grade 3/4 myelosuppression – severe sepsis occurred in ten patients (71%). Other grade 3/4 nonhematologic toxicities included hepatic transaminitis, oral mucositis, and diarrhea. Two patients (14%) developed hepatic venoocclusive disease (VOD).

Conclusions. The addition of Mylotarg to idarubicin and ara-C is feasible. MIA has significant activity in patients with refractory AML. Hepatotoxicity and VOD are significant toxicities of Mylotarg-based combinations.