Fludarabine, Cytarabine, Idarubicin and Etoposide (FLAIE) schedule is safe and active for young patients with newly diagnosed acute myeloid leukemia (AML): Results of a multicentric phase III Italian study

Background. Fludarabine plus Cytarabine and Idarubicine (FLAI) was proved to be an effective and well tollerated induction regimen for treatment of acute myeloid leukaemia (AML). The trial objective was to assess the efficacy of Etoposide when used in combination with FLAI schedule. Design and Methods. We retrospectively report clinical outcome results of 101 newly diagnosed and younger than 60 years AML patients (median age 46 years, range 18-60 years) treated in a Phase III clinical trial, with FLAIE induction chemotherapy, including Etoposide to the FLAI schedule. Induction consisted of Fludarabine 25mg/m2/day on days 1-5, Idarubicin 6 mg/m2/day on days 1, 3 and 5, Cytarabine 2 g/m2 infused in 4 h, daily on days1-5 and Etoposide 100 mg/m2/day on day 1-5. After induction, all the patients underwent consolidation with Cytarabine (2 g [[Unsupported Character – /]]sqm i.v. infusion on days 1-5) and Idarubicin (12 mg[[Unsupported Character – /]] sqm i.v. infusion on days 1, 3 and 5). All the patients shared the same strategy for intensification, that was allogenic or autologous stem cell transplantation. After consolidation, maintenance treatment with Cytarabine was given to patients who obtained a complete remission but who could not undergo allogenic or autologous stem cell transplantation. More than half of the patients had abnormal karyotypes. Molecular analysis at diagnosis for the more frequent abnormalities was performed. Duration of CR and overall survival was estimated according to the Kaplan-Meier method. The CR duration was dated from start of CR to first evidence of recurrence. Results. After a single induction course of FLAIE, 73 pts obtained a CR (72.2%) and 8 pts a CRp (7.9%) for an overall response rate of 80.2%. Fifteen patients (14.9%) had resistant disease, and 5 (4.9%) died during induction. After a median follow-up of 33 months, 75 patients (76%) are in continuous CR. The median CR duration and OS were 45 and 55 months, respectively. 11 pts underwent ABMT and 44 a BMT. Relapses were more frequent in patients who were not submitted to allogenic stem cell transplantation. Of the 55 transplanted patients, 28 (51.9%; 1 with chromosome 7 abnormality), were alive in CR after a median follow up of 10 months (range, 2 to 45 months) after transplantation, 14 (25.9%) relapsed (median DFS 4 months), and 13 (24%) died in CR or CRp of transplant related complications. The most common grade 3 adverse events included gastro-intestinal toxicities(i.e. nausea, vomiting, mucositis and diarrhoea), liver dysfunction, and skin rash. Conclusion. The combination of etoposide to FLAI is safe and active. Further studies exploring different dosing and scheduling are warranted, particularly in patients with poor-risk AML.