Gentuzumab-Ozogamicin (GO) Plus Idarubicin (I) and Cytarabine (C) as Induction Treatment for Elderly Patients with Poor-Risk Cytogenetics Acute Myeloid Leukemia (AML).

Introduction. The prognosis of AML in patients over 60 years of age remains very poor. As in younger patients karyotype is a major prognostic factor. Elderly patients with poor risk cytogenetics have a dismal outcome and complete remission (CR) rates with conventional chemotherapy are usually < 45% (and < 25% if complex abnormalities). GO has been used in combination with chemotherapy in relapsed or newly diagnosed AML, but with reduced doses in order to decrease hepatic toxicity.

Methods. In this multicentric open-label Phase II study we have evaluated the combination of I (8 mg/m²/D × D1-5) + C (100 mg/m²/D × D1-7) with GO (6 mg/m² on D3) in AML patients aged 60–75 years with poor risk cytogenetics and fit enough to undergo cytotoxic chemotherapy. Other inclusion criteria were: CD33+ AML, PS 2, de novo or secondary AML (excluding M3 and Ph1 + AML), no cardiac, renal or hepatic dysfunction.

Results. 44 pts aged 60–74 (median 68) were treated in 13 GOELAMS centers. Karyotype results were: chromosome (chr) 5 abnormalities 22, chr 7 abnormalities 26, chr 5+7 abnormalities 14, complex abnormalities 26. In 13 cases (30%) AML was secondary (chemoinduced 9, prior myeloproliferative or myelodysplastic syndrome 4). Median duration of hospitalisation was 31 D (4–51). In CR patients median duration of neutropenia was 19 D (14–28) and median duration of thrombocytopenia was 15D (5–29). Bacterial or fungal infections were documented in 71% of cases. 7 patients had severe bleeding including 3 deaths, (2 cerebral hemorrhage, 1 intestinal bleeding). Grade 2 hepatic dysfunction was seen in 30% of patients including 3 (7%) pts with veino-occlusive disease (one death). There were 17 (38%) CR (16 CR, 1 CRp), 6 (14%) toxic deaths and 21 (48%) failures. The CR rates was 41% (7/17) for patients aged 70–75 and 37% (10/27) for patients < 70 years. While CR rate was 50% (6/12) in patients with isolated chr 5 or 7 abnormalities, it was 35% (9/26) in patients with complex abnormalities.

Conclusion. In this population of elderly but relatively fit patients with poor risk cytogenetics AML the addition of GO 6 mg/m² to conventional chemotherapy did not appear to increase the CR rate mostly because of leukemic resistance. The incidence of aplasia-related toxicities and of hepatic complications does not encourage to use higher doses of GO.