Sequential administration of gemtuzubab ozogamicin (GO) and intensive chemotherapy for remission induction in previously untreated patients with AML over the age of 60: Interim results of the EORTC leukemia group AML-15A phase II trial

Gemtuzumab ozogamicin (CMA-676, Mylotargâ„¢), a conjugate of a humanized anti-CD33 monoclonal antibody linked to the cytotoxic antibiotic calicheamicin, has shown significant antileukemic activity in relapsed AML with a favorable side-effect profile. The EORTC-LG is performing a phase II study to determine the feasibility and activity of GO frontline therapy followed by intensive chemotherapy combining mitoxantrone, cytarabine and etoposide (MICE) as remission induction strategy for previously untreated elderly pts with standard risk (age 61-75 yrs and WHO PS grade 0/1) AML (FAB M3 excluded). GO was administered iv over 2 hrs at 9 mg/m2 for 2 doses on days 1 and 15. Within 7 days from response assessment to GO (between day 28 and 35 following last infusion, or sooner in case of leukemia progression), pts were starred on the MICE regimen (1 or 2 courses). Here we report the preliminary results from the 34 pts who are presently evaluable for response and toxicity. The median age was 68 yrs (range 61-73); 26 pts had primary AML and 8 secondary AML; CD33 positivity was documented in 30 pts (88%). Significant (grade 3/4 by NCI-CTC criteria) non-hematologic adverse events after GO included (33 pts evaluable): hypersensitivity syndrome (3%), hemorrhage (3%), DIC (6%). arrhythmia (6%). liver dysfunction and/or VOD (6%), febrile neutropenia (24%), infection (24%). A clinical response to GO was documented in 17 pts (50%); 9 (26.5%) achieved a complete remission (CR =