FLAG-(IDA)-Mylotarg in the Therapy of Relapsed and Refractory Acute Myeloid Leukemia.

Patients with relapsed and refractory AML have a bad prognosis. In this setting it is often difficult to obtain a complete remission. In the last few years fludarabine and high dose Citarabine with or without Idarubicine and G-CSF have been frequently used (FLAG and FLAG-IDA schedules). The immunotoxin gemtuzumab ozogamicin (Mylotarg)(GO) Wyeth is a humanized IgG4 monoclonal antibody directed against the CD33 epitope, which is chemically linked to calicheamicin, a highly potent antitumor antibiotic. As a single agent it has been shown to be an effective agent in the treatment of relapsed AML with a tolerable toxicity profile. Recently the United Kingdom Medical Research Council (MRC) published the preliminary results of AML15 trial, which was designed to evaluate the effect of adding GO to each course of intensive induction or consolidation chemotherapy in patients younger than 60 years as first-line treatment. These results are encouraging. We are using this association in the treatment of relapsed and refractory adult AML. Until now 10 patients have been enrolled in this trial and we show our preliminary results.

Patients and methods. 3 patients were resistant to induction; 3 patients were in the first relapse and 1 in the third after conventional chemotherapy, 1 was relapsed after autologous transplant and 2 were relapsed after allogeneic transplantation. The demography and characteristics are shown in the table. 8 Pts were treated with Fludarabine 30 mg/sqm dd 1–5, Citarabine 2,0 gr/sqm dd 1–5, Idarubicine 10 mg/sqm dd 3–5, Mylotarg 3 mg/sqm d −1, G-CSF 375 mg dd 1–6. 2 patients with the same schedule without Idarubicine.

Results: 6 patients obtained Complete Remission, 2 died after therapy and 2 were resistant to this schedule.Out of the 6 patients in CR 4 are in continuous complete remission at 3, 3, 8 and 11 months Three of these underwent allogeneic BMT with no significant toxicity and are actually in CR.. Two relapsed at 3 and 7 months. In our experience the toxicity of FLAG-(IDA)-GO schedule is acceptable and the results are promising in refractory and relapsed AML.