Background

The salvage therapy in patients with relapsed/refractory acute myeloid leukemia still poses a highly unmet clinical need. Given the established activity and toxicity profiles of hypomethylating agents such as 5-aza-2'-deoxycytidine (decitabine, DAC) in patients with untreated acute myeloid leukemia (AML), we explored the therapeutic effects of dose adjusted DAC in patients with relapsed / refractory AML, and compared treatment outcome with the conventional FLAG regimen.

Patients and Methods

27 patients with relapsed/refractory AML were included in this analysis. Twelve patients were treated with DAC 20 mg/m2 per day as 1-hour intravenous infusion for consecutive five days, with additional  1-3 doses of DAC added based on response and tolerability (Table 1). Another group of 15 patients received a course of FLAG regimen as controls.

Table 1

Adjustment for dose of DAC for relapsed/refractory acute myeloid leukemia

Characteristics Dose added 
Cellularity 0 
normal 1 
increased 0 
BM Blast % 1 
No 2 
<5% 0 
®5% -1 
General condition -1 
Karnofsky performance score®80 0 
Karnofsky performance score<80  
Age  
®60  
<60  
Characteristics Dose added 
Cellularity 0 
normal 1 
increased 0 
BM Blast % 1 
No 2 
<5% 0 
®5% -1 
General condition -1 
Karnofsky performance score®80 0 
Karnofsky performance score<80  
Age  
®60  
<60  
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Results

Although the overall response rates (ORR) were similar in DAC group (5/12) and FLAG group (9/15)£¨41.7 % versus 60 %, P=0.449£©, the complete remission (CR) rate plus CRi was lower in DAC group (2/12) than in FLAG group(10/15)£¨16.7 %versus 66.7 %, P=0.047£©. Induction mortality was 0 (0% at 8 weeks) and toxicities were manageable in both groups. Toxicities were predominantly hematologic. The most common drug-related adverse events (AEs£© were grade 4 myelosuppression which were comparable for DAC and FLAG., DAC group hadfewer infections£¨DAC, 6/12£»FLAG£€n=14/15, P=0.024£©. The 2-year survival rate was similar in the two groups: 25.0% in the DAC versus 26.7% in the FLAG group£¨P=0.574£©, while median survival times of the two groups were 4 and 12 months, respectively.

Conclusion

Dose-adjusted DAC achieved similar overall response rate with lower infection risk compared to FLAG regimen in patients with relapsed / refractory AML.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
decitabine, leukemia, myelocytic, acute, toxic effect, adverse event, complete remission, deoxycytidine, intravenous infusion procedures, myelosuppression, salvage therapy, frequency of responses

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2013 by The American Society of Hematology
2013
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