Poster Board I-49 Background: Current therapeutic strategies for the treatment of elderly acute myeloid leukemia (AML) patients are still unsatisfactory. Induction regimens relying on anthracycline and cytarabine combination (3+7) still represent the standard reference therapy, with complete remission (CR) rate of 35-60% but no more than 10-20% of patients living more than three years from diagnosis. The addition of other drugs to overcome resistance and prevent subsequent relapse, has often shown greater toxicity without improving results. Aim: We designed a phase II study aiming to assess toxicity and efficacy of My-FLAI regimen in patients with newly diagnosed AML aged more than 60 years. Fifty-one patients were enrolled with a median age of 68 years (range 60-76). The median leukocyte count was 10.2 x109/L (range 0.7-222.7). Twenty-five patients had a secondary AML and 31% had a complex kariotype. Fludarabine, cytarabine and idarubicin were administered for three consecutive days at the daily dose of 25 mg/m2, 1 g/ m2 and 5 mg/ m2 respectively. Gemtuzumab ozogamycin (Mylotarg, My) was infused at day four at the dose of 5 mg. Patients achieving a CR after the induction course were planned to receive a second identical course of My-FLAI. Granulocyte colony-stimulating factor (G-CSF) was administered at physician's discretion to promote granulocytic recovery if clinically indicated. Results: Twenty-seven patients achieved a CR (one of these with an incomplete platelet recovery) and 4 obtained a partial response (marrow blast 5-19%) for an overall response rate (ORR) of 61%. Seventeen patients (33%) showed a resistant disease and three (6%) died during induction (DDI). Seventeen patients received an identical consolidation course. Seven patients were treated with cytarabine-based consolidation and the remaining 27 patients were not treated furthermore. The disease-free survival (DFS) and overall survival (OS) were 6 months (range 2.4-48.0) and 13 months (range 1.1-61.5) respectively. DFS appear to be more favorable in patients receiving additional therapy after two My-FLAI cycles (IDAC n=3; ASCT n= 4; experimental drugs n= 1; My n=4) in comparison to patients no further treated, being 12.8 (range 4.7-18.0) and 5.9 (range 2.4-48.0) months respectively. The median duration of G-CSF administration was 6 days (range 0-35) in induction and 8 days (range 0-15) in consolidation cycle. All patients developed a grade IV hematological toxicity. Median time to ANC recovery (>1 x109/L) was 21 days (range 10-52) after induction course and 18 days (range 12-20) after consolidation course. Median time to PLT recovery (PLT>20 x109/L and PLT>100 x109/L) was 18 days (range 9-54) and 23 days (range 15-78) after induction and 18 days (range 12-20) and 32 days (range 21-110) after the consolidation course. Thirty-six patients had infectious complication; 33 experienced a microbiologically documented infection (n=20 gram+, n=12 gram- n=1 candidemia). Eighteen patients had a fever of unknown origin (FUO) and 12 patients suffered from pulmonary infection (n=2 bacterial; n=8 probable fungal; n=2 aspergillosis). One patient developed a maxillary sinus aspergillosis. Grade III/IV haemorrhagic complications were observed in 5 patients. No severe gastro-intestinal adverse events were observed. With a median follow-up of 8.8 months (range 0.5-61.5) 41 patients died. Five patients died in first CR for cardiac failure (n=2) and for infective complication (n=3). The remaining died for disease. Nine patients are alive, four of them in first CR. Conclusions: The four drug regimen My-FLAI is overall well tolerated in an elderly AML population. However, the efficacy did not appear to be superior to that of standard 3+7 regimen. Acknowledgments: Supported by BolognAIL, AIRC, European LeukemiaNET, COFIN, FIRB 2006, Fondazione del Monte di Bologna e Ravenna Disclosures: No relevant conflicts of interest to declare. Footnotes * Asterisk with author names denotes non-ASH members.
Full conference title:
51st American Society of Haematologists Annual Meeting
- ASH 51st (2009)