Azacitidine Plus Gemtuzumab Ozogamicin (GO): A Novel Combination in the Treatment of Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS) in the Elderly.

AML and high-risk MDS in the elderly carry a poor prognosis. Only 46% of AML patients receiving standard chemotherapy achieve complete remission (CR) and treatment-related mortality approaches 30% above age 60. In 2005, we initiated a Phase II trial for elderly patients with newly diagnosed AML or MDS, using the following outpatient treatment schema: If white blood cell (WBC) count at presentation was >10,000/ul, pt was started on hydroxyurea 1500 mg twice daily by mouth. Leukapheresis was performed if WBC >100,000/ul. Once WBC count was <10,000/ul, the patient received azacitidine 75 mg/m2 s/cu D1–7 and GO 3 mg/m2 on D8. A bone marrow was performed on D14 and induction therapy repeated for residual disease. Those who achieved CR were given one consolidation treatment with azacitidine+GO in same doses after recovery of blood counts. A total of 13 pts have been treated to date. Eleven had AML by WHO classification and 2 MDS (both RAEB). The median age was 77 (62–83) and 7 were male. Ten patients required retreatment on D14. Ten patients (76%) achieved CR. Six patients developed grade 3 toxicities: 5 neutropenic fever and 1 typhlitis, all requiring hospitalization. There were no treatment-related deaths. Median follow up is 7 months (2–13 months) and eleven patients remain alive. Two patients have died from relapsed or refractory disease. Nine patients remain in CR with a median duration of remission of 7 months (2–13 months). The trial is ongoing with an accrual goal of 20. Our early experience with this novel combination is quite encouraging. Cytoreduction with hydroxyurea and leukapheresis followed by azacitidine and GO appears to be a safe and effective regimen for elderly patients with AML and the therapy can be given in the outpatient setting. These preliminary results need to be confirmed in a larger cohort of patients.