Sequential administration of gemtuzumab ozogamicin and conventional chemotherapy as first line therapy in elderly patients with acute myeloid leukemia: a phase II study (AML-15) of the EORTC and GIMEMA leukemia groups.

BACKGROUND AND OBJECTIVES: Acute myeloid leukemia (AML) in the elderly is associated with low rates of response to conventional chemotherapy and long-term survival, highlighting the need for innovative treatment strategies. Gemtuzumab ozogamicin (GO) is an immunoconjugate that has shown activity in relapsed AML with a favorable safety profile. The aim of this collaborative trial was to assess the feasibility, safety, and antileukemic activity of administering GO followed by conventional chemotherapy as first line therapy in patients aged 61-75 years with AML. DESIGN AND METHODS: Eligible patients received frontline treatment with GO 9 mg/m2 infused intravenously on days 1 and 15. Following response assessment to GO, patients were started on conventional chemotherapy consisting of the MICE regimen (mitoxantrone, cytarabine, etoposide). No further treatment was planned for complete responders. RESULTS: Among the 57 evaluable patients, 38 (67%) completed the entire sequential treatment as planned. The overall response rate to the entire induction sequence was 54.4% (31/57), with complete remission (CR) in 35.1% and complete remission with incomplete platelet recovery (CRp) in 19.3%. Rates of failure due to treatment-related mortality or resistant disease were 14.1% (3 toxic deaths during the GO segment, 5 during MICE) and 29.9%, respectively. An initial response to GO was documented in 20 patients (35.1%), with CR in 22.8% and CRp in 12.3%; 6 additional patients entered a partial remission. Reversible myelosuppression and liver toxicity were the main adverse events during both segments of induction. Frontline GO was associated with modest mucosal and gastrointestinal toxicity, but grade 3-4 pancytopenia was universal and prolonged. Hepatic veno-occlusive disease developed in 3 patients after GO and 2 after MICE, resulting in 4 deaths from liver failure. One-year survival at follow-up was 34%. Twelve patients continue in CR/CRp after a median of 226 days. INTERPRETATION AND CONCLUSIONS: The sequential combination of GO and conventional chemotherapy is a feasible and active treatment strategy for older patients with untreated AML. This novel regimen is now being compared in a phase III trial (AML-17)